antibiotcs for research applications - sigma-aldrich

Peptides perturbing bacterial cell wall and extracting liposomal sphere, resulting in cell death.

Volume 4, Number 3

BioFilesLife Science

Antibiotics for Research Applications

Antimicrobial Peptides

Antifungals

New Antibiotics

Ready Made Solutions

Antibiotic Selector

2

Life Science

BioFilesVolume 4, Number 3

Table of Contents

Introduction 3

Antimicrobial Peptides 4

Bacteriocins 5

Insect RAMPs 5

Mammalian RAMPs 6

Bacterial Cell Killing Mechanisms 7

Antifungals 10

Antifungal Mechanisms of Action 10

Drug Resistance by Fungi 11

Antifungals that Bind Ergosterol or Inhibit Biosynthesis 12

Inhibits β-(1→3)Glucan Synthesis 13

Chitin Synthesis Inhibitors 13

Interferes with DNA, RNA, or Protein Synthesis 14

Additional Antifungal Compounds 15

New Antibiotics 16

Ready Made Solutions 19

Antibiotic Selector 21

Technical Content: Vicki Caligur, B.Sc. and Chloe McClanahan, B.Sc.

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Visit the Antibiotic Selector at sigma.com/antibiotics or see page 21 for additional information regarding this new online tool.

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IntroductionChloe McClanahanProduct Manager, [email protected]

This issue of BioFiles provides insight into antibacterial and antifungal resistance. Antifungal resistance may be just as alarming as antibacterial resistance. A reported mortality rate for patients with immunity inflicting diseases that

develop resistant fungal infections is 50–90%. Unfortunately, the elevated concern about resistance has not resulted in an abundance of antibiotics in the pharmaceutical pipeline due to high developmental costs and commercialization barriers. However, there is currently promising research being done to better understand the mechanisms and interactions of antimicrobial peptides and antifungal compounds in order to develop new, antibiotic drug candidates.

The article on page 4 provides an informative overview of the characteristics, mechanisms of action and types of ribosomally synthesized antimicrobial peptides (RAMPs) that either solely provide or contribute to the innate pathogenic defense system for many species. RAMPs are of growing interest because of continual RAMP discoveries and their lack of resistant isolates. The article on page 10 provides background information on the structural components of the fungal cell wall to aid in the understanding of the damaging functionality of antifungal compounds, along with a brief synopsis of drug resistance by fungal species. Antimicrobial peptides and antifungals available from Sigma® Life Science are found within this issue of BioFiles.

In addition to our antimicrobial peptides and antifungals, Sigma Life Science is continuously expanding our product offering based on research interest and customer demand. New antibiotic products are described on page 16, while our popular ready made antibiotic solutions are listed on page 19. If you have a new product suggestion for an antibiotic, please visit sigma.com/product_suggestions.

To help guide researchers in locating the most appropriate antibiotics, we have created the online Antibiotic Selector to aid in the selection and usability of research antibiotics. Please see page 21 for an Antibiotic Selector tutorial. Additionally, a companion selection poster with application, preparation, usage concentration, solution stability, and mechanistic information for the most commonly used research antibiotics is available. Please visit sigma.com/antibiotics to use the new Antibiotic Selector or request a poster.

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Antimicrobial PeptidesWith bacterial resistance and emerging infectious diseases becoming potential threats to humans, ribosomally synthesized antimicrobial peptides have become a promising focus area in antibiotic research. Antimicrobial peptides are classified as either non-ribosomally synthesized peptides or ribosomally synthesized peptides (RAMPs). Non-ribosomally synthesized peptides are found in bacteria and fungi. These antimicrobial peptides are assembled by peptide synthetases as opposed to ribosomal-supported synthesis. Gramicidin, bacitracin, polymyxin B, and vancomycin are examples of non-ribosomally synthesized antimicrobial peptides. These antibiotics are proven to be effective research tools, but compared to RAMPs they are disadvantageous for novel applications due to emerging bacterial resistance, for example vancomycin-resistant Staphylococcus aureus and enterococci.

RAMPs are derived from a diverse range of species, from prokaryotes to humans. Antimicrobial peptides comprise a host’s natural defense against the daily exposure to millions of potential pathogens. These peptides may also possess antiviral, antiparasitic, and antineoplastic activities. Over 500 RAMPs have been described in the literature. Their unique antibiotic spectrum is determined by amino acid sequence and structural conformation. RAMPs are gene-encoded peptides consisting of 12-50 amino acids with very little genetic overlap. A lack of sequence homology between RAMPs is indicative of evolutionary optimization of form and function in the species environment. RAMPs are typically cationic peptides with at least half of the amino acid residues being hydrophobic and a smaller number of neutral or negatively charged residues. Their amphipathic structure with opposing hydrophobic and lipohphilic faces aids in the perturbation of the bacterial cell wall.

The mechanism of action of a RAMP involves peptide binding to the bacterial cell surface, conformational change to the peptide, aggregation of multiple peptide monomers, and pore formation through the bacterial cell wall. RAMPs bind to lipopolysaccharides in the negatively-charged, Gram-negative bacterial outer cell wall or to the acidic polysaccharides of the Gram-positive bacterial outer cell wall. After binding, permeabilization of the bilayer membrane occurs by transient pore creation. Permeabilization leads to a leakage of cell components and cell death. There are several models of permeabilization although the precise mechanism is unknown. Three permeabilization models are termed barrel-stave, thoroidal, and carpet. Figure 1 depicts bacterial cell wall perturbation by a RAMP.

Figure 1. Antimicrobial peptide perturbation of the bacterial cell wall via the carpet model mode of action.

RAMPs are ideal candidates for clinical antimicrobial use because they:

1) Are active against antibiotic-resistant isolates

2) Do not select for resistant mutants and have limited natural bacterial resistance

3) Are synergistic with conventional antibiotics, specifically against resistant mutants

4) Are proven to kill bacteria in animal models

5) Kill rapidly

6) Provide benefical, supplementary activities, for example sepsis inhibition

Although RAMPs are ideal clinical candidates, their diverse structural variation makes it difficult to predict RAMP activity in vivo; therefore, it is challenging to design functional synthetic mimetics. Small changes in peptide sequence or conformation can lead to major in vivo differences in antimicrobial and cytotoxicity levels. An optimal in vitro minimum inhibitory concentration (MIC) against a range of bacterial organisms is 18 μg/ml. However, it is challenging to predict an ideal in vivo MIC from this in vitro MIC. In order to obtain MIC, specificity, stability and toxicity information, novel, synthetic antimicrobial peptides have been designed using data from RAMP-related, bioinformatic databases (see Table 1). Production costs, protease susceptibility, and potential resistance from widespread use are additional concerns in the transition of RAMP application from a research to clinical setting.

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Antimicrobial Peptide Databases Information Available Web Site

BAGELMolecular Genetics Dept., University of Groningen, The Netherlands

Bacteriocin genome location tool. http://bioinformatics.biol.rug.nl/websoftware/bagel/bagel_start.php

PhytAMPISSBAT Institute, Tunisia and INAF Institute, Laval University, Canada

Structural information and phylogenetic tree for ~270 natural, plant antimicrobial peptides.

http://phytamp.pfba-lab-tun.org/main.php

Antimicrobial Peptide Database, Version 2UNMC Eppley Cancer Center, University of Nebraska Medical Center, USA

Structural and functional information for 1,000+ antibacterial peptides.

http://aps.unmc.edu/AP/main.html

SAPDHaartman Institute, Helsinki University, Finland

Synthetic antibiotic peptide database. http://oma.terkko.helsinki.fi:8080/~SAPD

Defensins KnowledgebaseBioinformatics Institute, Singapore and Singapore Eye Research Institute

Sequence, structural and activity information for ~360 defensins.

http://defensins.bii.a-star.edu.sg/

Table 1. Antimicrobial Peptide Online Databases

BacteriocinsBacteriocins are non-pathogenic, antimicrobial peptides or proteins secreted by both Gram-positive and Gram-negative bacteria. Bacteriocins prevent the growth of similar bacterial strains but avoid damaging the host bacteria by selectively killing based on post-transcriptional modification and/or specific immunity mechanisms. Unlike the wide activity spectrum of conventional antibiotics, bacteriocins have a narrow activity spectrum. Additionally bacteriocins play a role in the regulation of signaling, virulence, and sporulation.

Nisin (Cat. No. N5764) is classified as a Class I, Type A lantibiotic. It is produced by Gram-positive, lactic acid fermentation bacteria and contains several atypical modified amino acids: thioether-bridged lanthionine, methyllanthionine, didehydroalanine and didehydroaminobutyric acid. Class I, Type A lantibiotics are elongated peptides that exhibit a range of activities including pore formation in bacterial bilayers while Class I, Type B lantibiotics are smaller, globular negatively charged or neutral peptides that inhibit specific enzymes. Class I, Type B lantibiotics include cinnamycin (Cat. No. C5241) and duramycin (Cat. No. D3168). An interesting subgroup of the non-lantibiotic bacteriocins is the Class IIa pediocin-like peptides. Pediocin (Cat. No. P0098) has been studied for its activity against pathogenic bacteria such as Listeria monocytogenes.

Although the genetic sequences of bacteriocins are not conserved, bacteriocin genes are often positioned near genes that aid in their production, for example transporter genes. BAGEL is a bacteriocin genome location tool developed and maintained by the Molecular Genetics Department at the University of Groningen, The Netherlands. This software is available for both academic and commercial use at http://bioinformatics.biol.rug.nl/websoftware/bagel/bagel_start.php.

Many of the bacteriocins are being studied for their application in food preservation. This methodology reduces requirements for potentially carcinogenic pesticides and heat treatments that reduce nutritional properties in food.

Bacteriocins may function as alternatives to conventional antibiotics that have been impacted by resistant strains. Millette, M. et al. recently demonstrated that nisin- and pediocin-producing bacteria reduced intestinal colonization by vancomycin-resistant Enterococci in vivo.

Insect RAMPsCecropin is a type of RAMP secreted within insects and active against Gram-negative bacteria. Cecropin A (Cat. No. C6830) is extracted from the hemolymph of the silk moth (Hyalophora cecropia) but has also been identified in porcine intestine. Antimicrobial peptides are often components of insect venoms, for example melittin from bee venom (Cat. No. M2272). It has been proposed that in primitive insect species RAMPs replace immune system processes, for example cytokine release, that characterize the bactericidal response in higher organisms. Drosophila synthesize different antimicrobial peptides in response to various infecting organisms. Kallio, J. et al. reported that RNAi targeting of several immune response genes in Drosophila caused altered antimicrobial peptide synthesis and identified involvement of the JNK signaling pathway in RAMP production.

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Mammalian RAMPsAlthough bacteriocins, insect, and mammalian RAMPs are similar in their bactericidal activity, the mammalian RAMPs also function as regulatory molecules in the host species’ immune response.

Defensins are a group of cationic, mammalian RAMPs that are commonly found on the skin, ear, epithelium, tongue, lung, and other surfaces frequently exposed to environmental pathogens. Phagocytic and epithelial cells, lymphocytes, and keratinocytes produce defensins. Figure 2 is an immunohistochemical staining of defensin-5 within respiratory epithelial cells using Prestige Antibodies® Anti-DEFA5 antibody, produced in rabbit (Cat. No. HPA015775). Defensins are constitutively expressed and stored in granules without external stimuli. However, increased levels of expression may be induced by proinflammatory cytokines, exogenous bacterial or LPS treatment.

Like the bacteriocins, defensins consist of variable amino acid residue composition. The two classes of defensins are defined by structure. The human α-defensins have three intramolecular cysteine bonds whereas the larger β-defensins (Cat. Nos. D9565, β-defensin 1 and D9690, β-defensin 2) consist of three anti-parallel β-sheets and a unique disulfide bridge pattern connecting six cysteine residues. In addition to antimicrobial and antiviral activities, α-defensins inactivate LPS binding, regulate complement activation, and function as an adjuvant in mice. β-defensins induce prostaglandin production and play a regulatory role in the adaptive immune responses by functioning as chemoattractants for T lymphocytes as well as for immature dendritic cells via signaling through a chemokine receptor.

Figure 2. Immunohistochemical staining of human nasopharynx shows cytoplasmic and membranous positivity in respiratory epithelial cells using Prestige Antibodies® Anti-DEFA5 (Cat. No. HPA015775).

References:Pag, U. et al., In vitro activity and mode of action of diastereometric antimicrobial peptides against bacterial clinical isolates. JAC, 53, 230-239 (2004).Papagianni, M., Ribosomally synthesized peptides with antimicrobial properties: biosynthesis, structure, function, and applications. Biotech. Advances, 21, 465-499 (2003).Gunn, J.S., Bacterial modification of LPS and resistance to antimicrobial peptides. J. Endotoxin Res., 7, 57-62 (2001).Nicholson, J.K. et al., The challenges of modeling mammalian biocomplexity. Nat. Biotechnol., 22, 1268-1274 (2004).Palffy, R. et al., On the physiology and pathophysiology of antimicrobial peptides. Mol. Med., 15, 51-59 (2009).Hancock, R. and Chapple, D., Peptide antibiotics. Antimicrob. Agents Chemother., 43, 1317-1323 (1999).Hancock, R. and Scott, M. The role of antimicrobial peptides in animal defense. PNAS, 97, 8856-8861 (2000).Drider, D. et al., The continuing story of class IIa bacteriocins. Microbiol. Mol. Biol. Rev., 70, 564-582 (2006).Holtsmark, I. et al., Bacteriocins from plant pathogenic bacteria. FEMS Microbiol. Lett., 280, 1-7 (2007).Chen, H. and Hoover, D.G. Bacteriocins and their food applications. Comprehensive Reviews in Food Science and Food Safety, 2, 82-100 (2003).Galvez, A. et al., Application of bacteriocins in the control of foodborne pathogenic and spoilage bacteria. Crit. Rev. Biotechnol., 28, 125-152 (2008).Galvez, A. et al., Bacteriocin-based strategies for food biopreservation. Int. J. Food Microbiol., 120, 51-70 (2007).Brumfitt, W. et al., Nisin, alone and combined with peptidoglycan-modulating antibiotics: activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. J. Antimicrob. Chemother., 50, 731-734, (2002).Millette, M et al., Capacity of human nisin- and pediocin-producing lactic acid bacteria to reduce intestinal colonization by vancomycin-resistant enterococci. Appl. Environ. Microbiol., 74, 1997-2003 (2008).Montesinos, E., Antimicrobial peptides and plant disease control. FEMS Microbiol. Lett., 270, 1-11 (2007).Buckling, A. and Brockhurst, M. Microbiology: RAMP resistance. Nature, 438, 170-171 (2005).Kallio, J. et al., Functional analysis of immune response genes in Drosophila identifies JNK pathway as a regulator of antimicrobial peptide gene expression in S2 cells. Microbes and Infection, 7, 811-819 (2005).Komatsuzawa, H. et al., Innate defences against methicillin-resistant Staphylococcus aureus (MRSA) infection. J. Pathol., 208, 249-260 (2006).Meade, K.G. et al., Directed alteration of a novel bovine β-defensin to improve antimicrobial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Int. J. Antimicrob. Agents, 32, 392-397 (2008).Oppenheim, J.J. et al., Roles of antimicrobial peptides such as defensins in innate and adaptive immunity. Ann. Rheum. Dis., 62, ii17-ii21 (2003).Yang, D. et al., The role of mammalian antimicrobial peptides and proetins in awakening of innate host defenses and adaptive immunity. Cell Mol. Life Sci., 58, 978-989 (2001).Yang, D. et al., β-Defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science, 286, 525-528 (1999).




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Bacterial Cell Killing MechanismsThe diversity of structure within antimicrobial peptides results in an essential, innate defense system for both simple and complex organisms. Although the antimicrobial peptides have unique structural properties, they can be simply categorized by their killing action. Antimicrobial peptides typically use one of the following killing mechanisms: cell membrane interference, cell wall synthesis interference, protein synthesis interference, protein inhibition and nucleic acid inhibition.

Cell Membrane Interference

Name Description Cat. No.

Cecropin A, ≥97% (HPLC), powder Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. C6830-.1MGC6830-.5MG

Cecropin B, ≥97% (HPLC), powder Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. C1796-.1MGC1796-.5MG

Cecropin P1 Porcine, ≥95% (HPLC), powder Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. C7927-.1MGC7927-.5MG

Cinnamycin, >95% (HPLC), solid Cinnamycin (Ro 09-0198) is a tetracylic peptide antibiotic (19 amino acids) that binds specifically to the cell surface phosphatidylethanolamine and subsequently induces cytolysis. This is a rare example of a small peptide binding to a particular lipid (1:1 complex). Cinnamycin belongs to the duramycin-type lantibiotics and contains the unusual thioether lanthionine amino acids.

C5241-1MG

Colistin sulfate salt, activity: ≥15,000 units/mg Mode of Action: Binds to lipids on the cell cytoplasmic membrane of Gram-negative bacteria and disrupts the cell wall integrity.Antimicrobial spectrum: Gram-negative bacteria.

C4461-100MGC4461-1G

Colistin sodium methanesulfonate, activity: ~11,500 units/mg

Mode of Action: Binds to lipids on the cell cytoplasmic membrane of Gram-negative bacteria and disrupts the cell wall integrity.Antimicrobial spectrum: Gram-negative bacteria.

C1511-10MUC1511-100MU

Colistin sodium methanesulfonate, BioChemika, from Bacillus colistinus

Mode of Action: Binds to lipids on the cell cytoplasmic membrane of Gram-negative bacteria and disrupts the cell wall integrity.Antimicrobial spectrum: Gram-negative bacteria.

27655-1G27655-5G

Defensin HNP-1 human, ≥80% (HPLC) This is an endogenous antibiotic peptide and monocyte chemotactic peptide produced by human neutrophils. Defensins are a family of 3-4 kDa (29-34 amino acids) peptides found in the granules of mammalian phagocytes. The members of this family are variably arginine-rich and share six conserved cysteine residues that participate in intramolecular disulfide bonds.

D2043-25UG

Defensin HNP-2 human, ≥95% (HPLC) This is an endogenous antibiotic peptide and monocyte chemotactic peptide produced by human neutrophils. Defensins are a family of 3-4 kDa (29-34 amino acids) peptides found in the granules of mammalian phagocytes. The members of this famuly are variably arginine-rich and all share 6 conserved cysteine residues that participate in intramolecular disulfide bonds.

D6790-25UG

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Indolicidin, ≥97% (HPLC) Exhibits potent antimicrobial activity in vitro against bacteria and fungi. I0144-.1MG

Magainin I, ≥97% (HPLC) Antibiotic peptide. Thought to preferentially bind to anionic phospholipids abundant in bacterial membranes with the formation of dynamic peptide-lipid supramolecular pore and cell permeabilization, magainins are positively charged and amphiphatic. Binding to artificial neutral membranes has also been demonstrated.

M7152-.1MGM7152-.5MGM7152-1MG

Magainin II, ≥97% (HPLC) Antibiotic peptide. Magainins are positively charged and amphiphatic. Thought to preferentially bind to anionic phospholipids abundant in bacterial membranes with the formation of dynamic peptide-lipid supramolecular pore and cell permeabilization. Binding to artificial neutral membranes has also been demonstrated.

M7402-.1MGM7402-.5MGM7402-1MG

Nisin from Lactococcus lactis, 2.5% (balance sodium chloride and denatured milk solids)

Antibiotic with bactericidal action on E. coli. Binds to the lipid A portion of bacterial lipopolysaccharides. Induces pore formation in the membranes of cortex cells from excised sorghum roots.Mode of Action: Binds to and interferes with the permeability of the cytoplasmic membrane.Antimicrobial spectrum: Gram-negative bacteria.

N5764-1GN5764-5GN5764-25G

Pediocin from Pediococcus acidilactici, ≥95% (HPLC), buffered aqueous solution 8

Pediocins are class IIa bacteriocins that are produced by Pediococcus sp. They are cationic peptides that show strong activity against pathogenic bacteria such as Listeria monocytogenes, Clostridicum perfringes, Enterococcus faecalis, and Staphylococcus aureus. This antimicrobial action of pediocins is based on interaction with the cytoplasmic membrane, resulting in pore formation and cell death.

P0098-50UG

Polymyxin B solution, BioChemika, 1 mg/mL in H2O

- 81271-10ML

Polymyxin B sulfate, meets USP testing specifications, powder


P0972-1MUP0972-10MUP0972-50MU

Polymyxin B sulfate salt, activity: ≥6,000 USP units/mg


P1004-1MUP1004-5MUP1004-10MUP1004-25MUP1004-50MU

Polymyxin B sulfate salt, powder, cell culture tested


P4932-1MUP4932-5MU

Polymyxin B sulfate salt, Biotechnology Performance Certified


P4119-10MUP4119-25MUP4119-50MU

Valinomycin, ≥98% (TLC), ≥90% (HPLC), solid K+-selective ionophoric cyclodepsipeptide; potassium ionophore which uncouples oxidative phosphorylation, induces apoptosis in murine thymocytes, inhibits NGF-induced neuronal differentiation and antagonizes ET-induced vasoconstriction.

V0627-10MGV0627-25MGV0627-100MGV0627-500MG

Valinomycin, BioChemika, ≥98.0% (TLC) K+-selective ionophoric cyclodepsipeptide; potassium ionophore which uncouples oxidative phosphorylation, induces apoptosis in murine thymocytes, inhibits NGF-induced neuronal differentiation and antagonizes ET-induced vasoconstriction.

94675-10MG94675-100MG94675-500MG

Valinomycin, Ready Made Solution, ~1 mg/mL in DMSO, 0.2 μm filtered

K+-selective ionophoric cyclodepsipeptide; potassium ionophore which uncouples oxidative phosphorylation, induces apoptosis in murine thymocytes, inhibits NGF-induced neuronal differentiation and antagonizes ET-induced vasoconstriction.

V3639-5ML

Cell Wall Synthesis Interference


Bacitracin, from Bacillus licheniformis, activity: ≥50,000 U/g

Peptide antibiotic.Antimicrobial spectrum: Gram-positive bacteria.Mode of Action: Inhibits bacterial cell wall synthesis by inhibiting dephosphorylation of lipid pyrophosphate.

B0125-50KUB0125-250KUB0125-1250KU

Bacitracin, from Bacillus licheniformis, BioChemika, activity: ≥60000 U/g (Potency)


11702-5G11702-25G

Bacitracin zinc salt, from Bacillus licheniformis, activity: ~70,000 U/g


B5150-250KUB5150-1250KU

Vancomycin hydrochloride from Streptomyces orientalis, potency: ≥900 μg per mg (as vancomycin base)

Glycopeptide antibioticMode of action: interferes with cell wall synthesisAntimicrobial spectrum: Gram-positive bacteria

V2002-100MGV2002-250MGV2002-1GV2002-5G

Vancomycin hydrochloride from Streptomyces orientalis, Biotechnology Performance Certified

Glycopeptide antibioticMode of action: interferes with cell wall synthesisAntimicrobial spectrum: Gram-positive bacteria

V1764-250MGV1764-1G

Cell Membrane Interference, continued




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Protein Synthesis Interference or Inhibition


Actinonin Inhibitor of leucine aminopeptidase. A6671-10MGA6671-25MG

Amastatin hydrochloride hydrate, ≥97% (HPLC) Amastatin is a slow, tight-binding inhibitor of aminopeptidases. It inhibits cytosolic leucine aminopeptidase (EC.3.4.11.1), microsomal aminopeptidase M (EC.3.4.11.2) and bacterial leucine aminopeptidase (EC.3.4.11.10). It is less effective against aminopeptidase A (EC 3.4.11.7), the enzyme that converts Angiotensin II to Angiotensin III. Effective concentration: 1-10 μM.

A1276-250UGA1276-.5MGA1276-1MGA1276-5MGA1276-10MGA1276-25MG

Antimycin A from Streptomyces sp. Inhibitor of electron transfer at complex III. Induces apoptosis. A8674-25MGA8674-50MGA8674-100MG

Antipain dihydrochloride from microbial source Isolated from a microbial source, antipain hydrochloride is a reversible inhibitor of serine/cysteine proteases and some trypsin-like serine proteases. Its action resembles leupeptin; however, its plasmin inhibition is less and its cathepsin A inhibition is more than that observed with leupeptin.

A6191-1MGA6191-5MGA6191-25MGA6191-100MG

Duramycin from Streptoverticillium cinnamoneus, 90-95%

Polypeptide antibiotic which enhances chloride secretion in airway epithelium; used in studies of cystic fibrosis

D3168-10MG

Elafin human, >90% (by MS, HPLC and SDS-PAGE), recombinant, expressed in Saccharomyces cerevisiae

Exhibits co-existant antimicrobial and antiproteolytic activities.Antimicrobial spectrum: Gram-positive and Gram-negative bacteria.

E7280-100UG

Gramicidin A from Bacillus brevis, BioChemika, ≥90% (HPLC)

Gramicidin A is a polypeptide antibiotic that forms single ion monovalent cation channels in biological membranes.

50845-100MG50845-500MG

Gramicidin from Bacillus aneurinolyticus (Bacillus brevis), Linear polypeptide antibiotic complex. A mixture of gramicidins A, B, C, and D.

Linear polypeptide antibiotic, a mixture of gramicidin A, B, C, and D. Gramicidin D, a channel-forming ionophore that flip-flops slowly across the membrane is a known Pgp substrate and surprisingly was found to inhibit Pgp ATPase activity. This inhibition was reversed by other Pgp substrates suggesting a common drug binding site among MDR substrate-type drugs and chemosensitizers.

G5002-100MGG5002-500MGG5002-1GG5002-5G

Gramicidin C from Bacillus brevis, BioChemika, ~90% (HPLC)

Naturally occuring polypeptide antibiotic with Tyr at position 11; functions as a transmembrane ion channel. 50847-10MG50847-50MG

Thiostrepton from Streptomyces azureus, ≥90% (HPLC)

Peptide antibiotic that prevents the binding of elongation factor G (EF-G) and GTP to the 50S ribosomal subunit.

T8902-1G

Nucleic Acid Inhibition


Actinomycin D, from Streptomyces sp., ~98% (HPLC)

An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. For cell culture applications, actinomycin D is used as a selection agent and is used in banding techniques to differentiate between different regions of chromosomes.

A1410-2MGA1410-5MGA1410-10MGA1410-25MGA1410-100MG

Actinomycin D, from Streptomyces sp., ~95% (HPLC)


A4262-2MGA4262-5MGA4262-10MGA4262-25MG

Actinomycin D, ≥95%, from Streptomyces sp., cell culture tested

An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. For cell culture applications, actinomycin D is used as a selection agent and is used in banding techniques to differentiate between different regions of chromosomes.Mode of Action: Complexes with DNA and interferes with RNA synthesis.

A9415-2MGA9415-5MGA9415-10MGA9415-25MG

Actinomycin D–Mannitol, lyophilized powder 1 mg actinomycin D and 49 mg mannitol per vial


A5156-1VL

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AntifungalsAntifungal compounds have been overshadowed by antibacterials in research interest and application due to the greater impact bacterial infections have had on health. Resistance to antibacterial drugs and the resultant clinical impact is of widespread concern regarding public health. However, resistance by pathogenic fungal infections to drug treatment has become more common in the last 20 years as well. Some mechanisms of the development of fungal resistance have similarities to those of the development of drug resistance in bacteria, and knowledge of those bacterial mechanisms is being applied to understanding fungal drug resistance.

Several key antibiotic compounds function by targeting the integrity of the cell. Many compounds increase the porosity of the cell wall or membrane, or interfere with key steps in the synthesis of cell walls. While prokaryotic bacteria and eukaryotic fungi do not have identical cell wall and membrane components, there are corresponding lipids and key structural molecules. As a result, similar to antibacterials, most antifungal compounds work because they directly or indirectly damage the cell wall or cell membrane.

The fungal cell wall is composed of multiple layers, with mannoproteins being predominantly expressed at the external surface (see Figure 1). An underlayer of β-glucan creates a supporting matrix for the mannoproteins and provides structural rigidity to the cell wall. The glucan structure is strengthened by frequent β(1→3) and additional β(1→6) linkages and by chitin interspersed with the β-glucan. Mannoproteins and glucan make up more than 80% of the cell wall composition, while chitin represents less than 2%. The plasma membranes of fungi are primarily composed of ergosterol, analogous to cholesterol in animal cells. Since ergosterol and cholesterol have sufficient structural differences, the majority of chemicals found to act as fungicides target ergosterol biosynthesis or cell membrane porosity and do not cross react with host cells.

Yeast Cell Wall

Mannoprotein

Mannoprotein

Membrane

β-Glucan + Chitin

β-Glucan

Figure 1. Structure of the yeast cell wall. The wall is primarily composed of mannoproteins and β-glucan that is linked (1→3) and (1→6). Ergosterol is the major lipid component of the underlying plasma membrane.

Antifungal Mechanisms of ActionSeveral reviews of antifungal compounds group them into structural classes and have associated certain structures with particular modes of actions. Examples of some of the key structures of fungicides are shown in Figure 2. The binding and synthesis of ergosterol, the major cell membrane component, are the targets for several antifungal structures. The azoles and triazoles interfere with the ergosterol biosynthesis pathway by inhibiting cytochrome P450-dependent 14α-demethylase and blocking the oxidative removal of 14α-methyl from lanosterol. This incomplete processing of lanosterol results in an increase in ergosterol precursors and a decrease in ergosterol, leading to structural changes in the lipid membrane. Azoles have also been reported to inhibit membrane-surface enzymes and lipid biosynthesis.

Allylamines, of which terbinafine (Cat. No. T8826) is the most common example, also block ergosterol biosynthesis, but at an earlier step. Terbinatine inhibits the enzyme squalene epoxidase, which participates in the conversion of squalene to lanosterol. The resulting build-up of squalene is toxic to the fungal cell. A third structural class, polyenes, increases the permeability of the plasma membrane. Amphotericin B (Cat. No. A4888), a polyene with high affinity for sterol binding, is one of the most potent antifungal drugs; its mechanism produces pores in the membrane surface of the yeast, resulting in leakage of the cell contents. (Odds, et al., 2003).

F

FNN N

OH

NN

N

NCH3 H

HCH3

CH3CH3

• HCl

HO

CH3

OH OH OH

OH

COOHO

CH2

OH

O

OH

OHH3CH2N

O

H

O

O

OH

OH

CH3

CH3

Nystatin A1

NO

O

CH3

OH

NHN

NHO

H3C

HO

ON

NHOH3C

OH

H

OH

H

H

HHHO OH

HO

H

NH CO (CH2)14CH3

O

H H

HO

H

HHO

Figure 2. Examples of antifungal structure classes. a. Fluconazole (triazole) b. Terbinafine (allylamine) c. Nystatin A1 (polyene) d. Aculeacin A (echinocandin).

Yeast Cell Wall

a.

b.

c.

d.




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In addition to the plasma membrane and its lipid surface, fungicidal compounds may damage the cell wall of yeast. The major cell wall component β(1→3) glucan is the target of echinocandins and aculeacins such as aculeacin A (Cat. No. A7603). Echinocandins are semisynthetic lipopeptides that competitively inhibit β-glucan synthetase; the mechanism of action is not well defined but does not involve cytochrome P450 inhibition or P-glycoprotein transport (Kauffman and Carver, 2008).

Chitin is a trace, critical component of the fungal cell wall, and some inhibitors of chitin synthesis demonstrate antifungal activity. Members of this family of antifungals (i.e., polyoxins and nikkomycins) have structures analogous to UDP-N-acetyl-D-glucosamine (UDP-GlcNAc). This nucleoside phosphate is a glycosyl donor substrate for chitin synthesis, and the antifungals act as competitive substrates to inhibit chitin synthetase (Hector, 1993).

Not all antifungal compounds have known mechanisms of action, and some of them are relatively unique. While there are several antibacterials that function by preventing DNA or RNA replication, 5-fluorocytosine (Cat. No. F7129) is a novel antifungal in that its mechanism of action involves blocking DNA synthesis and inhibiting thymidylate synthetase. Sordarin (Cat. No. S1442) is one of the few compounds that selectively inhibit fungal protein synthesis. Other antifungal antibiotics target sphingolipid biosynthesis and electron transport (Gupte, et al., 2002). The mode of action of griseofulvin (Cat. No. G4753) is not completely clear, but it has been speculated that griseofulvin inhibits microtubule binding within the mitotic spindle, weakening the cell structure (Odds, et al., 2003).

Drug Resistance by FungiDrug resistance in fungi, especially to azoles, is becoming more prevalent clinically, and the mechanisms of drug resistance are similar to those present in bacteria. Several factors contribute to multidrug resistance in yeasts, including the mutation of genes and overexpression of proteins that act as efflux pumps (Monk and Goffeau, 2008). Fungi contain both ATP-binding cassette (ABC) transporter and major facilitator superfamily (MFS) transporter gene families.

The multidrug resistance process for fungi has been most analyzed for Saccharomyces cerevisiae, where it is called pleiotropic drug resistance (PDR) (Rogers, et al., 2001). In S. cerevisiae, point mutations occur in the genes for the transcription regulatory factors Pdr1p and Pdr3p. These mutations (called “gain-of-function” mutations) activated downstream target genes, including the ABC transporter genes and MFS transporter genes. The products of these genes are efflux pumps that transport drug compounds out of the cell, reducing the intracellular concentration to a sublethal level.

Some research reports on antifungals have found greater efficacy with combinations of antifungal drugs that use different mechanisms of action. The same process has been applied to other compounds in looking for ways to overcome fungal resistance. A variety of immunosuppressive compounds, including cyclosporin and D-octapeptides (Monk, et al., 2005), have been tested and found to counteract antifungal resistance due to efflux pumps. Cernicka, et al. screened a synthetic compound library and identified a chemical that increased the sensitivity of a drug-resistant strain of S. cerevisiae to fluconazole (Cernicka, et al., 2007). The compound also increased sensitivity of the pathogenic yeasts Candida albicans and Candida glabrata that expressed efflux pumps.

As drug resistance continues to develop in pathogenic fungi, there will be research to find ways to circumvent resistance and identify next-generation drugs. Understanding the cellular processes and resistance pathways can be applied to finding alternative compounds to the well-established azoles that are the prime targets of fungal efflux.

References:Cernicka, J., et al., Chemosensitisation of drug-resistant and drug-sensitive yeast cells to antifungals. Int. J. Antimicrob. Agents, 29, 170-8 (2007).Ghannoum, M.A. and Rice, L.B. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin. Microbiol. Rev., 12, 501-17 (1999).Gupte, M., et al., Antifungal antibiotics. Appl. Microbiol. Biotechnol., 58, 46-57 (2002).Hector, R.F. Compounds active against cell walls of medically important fungi. Clin. Microbiol. Rev., 6, 1-21 (1993).Kauffman, C.A. and Carver, P.L. Update on echinocandin antifungals. Semin. Respir. Crit. Care Med., 29, 211-9 (2008).Katzmann, D.J., et al., Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5. J. Biol. Chem., 271, 23049-54 (1996).Monk, B.C., et al., Surface-active fungicidal D-peptide inhibitors of the plasma membrane proton pump that block azole resistance. Antimicrob. Agents Chemother., 49, 57-70 (2005).Monk, B.C. and Goffeau, A. Outwitting multidrug resistance to antifungals. Science, 321, 367-8 (2008).Odds, F.C., et al., Antifungal agents: mechanisms of action. Trends Microbiol., 11, 272-9 (2003).Rogers, B., et al., The pleitropic drug ABC transporters from Saccharomyces cerevisiae. J. Mol. Microbiol. Biotechnol., 3, 207-14 (2001).Vanden Bossche, H., et al. Antifungal drug resistance in pathogenic fungi. Med. Mycol., 36, Supp. 1.,119-28 (1998).

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Antifungals that Bind Ergosterol or Inhibit BiosynthesisName Description Cat. No.

Amphotericin B from Streptomyces sp., ~80% (HPLC), powder

Polyene antifungal antibiotic from Streptomyces. Affinity for sterols, primarily ergosterols, of fungal cell membranes. Forms channels in the membranes, causing small molecules to leak out. Antimicrobial spectrum: fungi and yeast.

A4888-100MGA4888-250MGA4888-500MGA4888-1GA4888-5GA4888-100G

Amphotericin B from Streptomyces sp., ~80% (HPLC), cell culture tested

Polyene antifungal antibiotic from Streptomyces. Affinity for sterols, primarily ergosterols, of fungal cell membranes. Forms channels in the membranes, causing small molecules to leak out. Antimicrobial spectrum: fungi and yeast.

A2411-250MGA2411-1GA2411-5G

Amphotericin B solubilized, powder, γ-irradiated, cell culture tested

Polyene antifungal antibiotic from Streptomyces. Affinity for sterols, primarily ergosterols, of fungal cell membranes. Forms channels in the membranes, causing small molecules to leak out. Antimicrobial spectrum: fungi and yeast.Mode of Action: Interferes with fungal membrane permeability by forming channels in the membranes and causing small molecules to leak out.

A9528-50MGA9528-100MGA9528-500MGA9528-1GA9528-5G

Amphotericin B solution, sterile-filtered, 250 μg/mL in deionized water, cell culture tested

Mode of action: Interferes with fungal membrane permeability by forming channels in the membranes and causing small molecules to leak out.Antimicrobial spectrum: Yeasts and molds.

A2942-20MLA2942-50MLA2942-100ML

Cerulenin, ~95%, from Cephalosporium caerulens

Antibiotic and antifungal. Mode of action: Inhibits fatty acid synthetases, blocking production of fatty acids and sterols in both fungi and eukaryotes.

C2389-5MGC2389-10MGC2389-50MG

Clotrimazole Specific inhibitor of Ca2+-activated K+ channels. Antifungal azole. Antifungal mode of action: Inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, altering cell membrane permeability.

C6019-5GC6019-25GC6019-100G

Dermaseptin from Phyllomedusa sauvagii, ≥97% (HPLC)

Dermaseptin is a cationic, amphipathic antifungal peptide. Mode of action: Lysis of the cell membrane by interaction with membrane lipids. Highly potent antifungal activity at micromolar concentration.

D4671-.1MGD4671-.5MG

Econazole nitrate salt Econazole is an azole-based antifungal similar to ketoconazole. Its mechanism of action may involve inhibition of membrane enzymes, including cytochrome P450, and lipid biosynthesis. The bactericidal and inhibitory effects of several azole antifungal compounds, including econazole, against Mycobacterium smegmatis has been investigated.

E4632-5GE4632-25GE4632-100G

Filipin complex from Streptomyces filipinensis, ≥70% (UV)

Filipin is a polyene macrolide antibiotic and antifungal. The antifungal mechanism of action is unclear but may be due to altering membrane permeability and associated functions via binding to membrane sterols. Filipin binds to membrane sterols such as cholesterol, and it both inhibits prion protein (PrP) endocytosis and causes the release of PrP from the plasma membrane.

F9765-25MGF9765-50MG

Fluconazole, ≥98% (HPLC), solid Fluconazole is an antifungal agent. It is highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethyllation. Fluconazole is a potent inhibitor of CYP2C9. Fluconazole interferes with fungal ergosterol synthesis and downregulates the metallothionein gene.

F8929-100MG

Itraconazole, ≥98% (TLC) Synthetic broad-spectrum triazole antifungal agent. Mode of action: Inhibits cytochrome P450 dependent enzymes including 14α-demethylase. The inhibition results in prevention of the biosynthesis of ergosterol, a critical fungal cell wall component in fungi.

I6657-100MG

Ketoconazole, ≥98% (TLC) First generation antifungal azole. Mode of action: Inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, resulting in an altered cell membrane permeability.

K1003-100MGK1003-1G

(±)-Miconazole nitrate salt Antifungal azole. Mode of action: Inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, resulting in an altered cell membrane permeability. Also inhibits peroxidases, which results in accumulation of peroxide within the cell.

M3512-1GM3512-5GM3512-25G

Nystatin preparation, suspension, sterile; aseptically processed, cell culture tested

Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols.Antimicrobial spectrum: Yeasts and molds.

N1638-20MLN1638-100ML

Nystatin, activity: ≥4,400 USP units/mg Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols.Antimicrobial spectrum: Yeasts and molds.

N3503-5MUN3503-25MU

Nystatin, powder, cell culture tested Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols.Antimicrobial spectrum: Yeasts and molds.

N6261-500KUN6261-5MUN6261-25MU

Nystatin, powder, γ-irradiated, cell culture tested

Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols.Antimicrobial spectrum: Yeasts and molds.

N4014-50MG

Pimaricin preparation, ~2.5%, aqueous suspension

An antifungal polyene macrolide that binds specifically to ergosterol and blocks fungal growth. However, unlike nysatin and filipin, pimaricin does not change the permeability of the plasma membrane.

P0440-20ML

Pimaricin preparation, BioChemika, aqueous suspension 2.5%, sterile, ~90% (N)

An antifungal polyene macrolide that binds specifically to ergosterol and blocks fungal growth. However, unlike nysatin and filipin, pimaricin does not change the permeability of the plasma membrane.

80482-20ML
































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Pimaricin, from Streptomyces chattanoogensis, ≥95% (HPLC)

An antifungal polyene macrolide that binds specifically to ergosterol and blocks fungal growth. However, unlike nysatin and filipin, pimaricin does not change the permeability of the plasma membrane

P9703-25MGP9703-50MGP9703-100MG

Staurosporine from Streptomyces sp., ≥95% (HPLC), solid

Partially reverses MDR, sensitizing cells with MDR phenotype to cytotoxic agents. Inhibits Pgp phosphorylation. However, functional significance of Pgp phosphorylation is ill defined. Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells.

S4400-.1MGS4400-.5MGS4400-1MG

Staurosporine from Streptomyces sp., for molecular biology, ≥95% (HPLC)

Partially reverses MDR, sensitizing cells with MDR phenotype to cytotoxic agents. Inhibits Pgp phosphorylation. However, functional significance of Pgp phosphorylation is ill defined. Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells.

S5921-.1MGS5921-.5MGS5921-1MG

Staurosporine solution from Streptomyces sp., Rready Made Solution, 1 mM in DMSO (100 μg/214 μL), 0.2 μm filtered

Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells.Potent cell-permeable inhibitor of protein kinase C. Induces apoptosis in Jurkat cells.

S6942-200UL

Terbinafine hydrochloride, ≥98% 8 Mode of Action: Inhibits squalene epoxidase, preventing biosynthesis of ergosterol.Antimicrobial spectrum: Antifungal and antimycotic. Fungicidal against dermatopytes and some yeasts; fungistatic against Candida albicans.

T8826-100MGT8826-250MG

Zomepirac sodium salt - Z2625-250MGZ2625-1GZ2625-5G

Inhibits β-(1→3)Glucan SynthesisName Description Cat. No.

Aculeacin A, from Aspergillus aculeatus, ≥95% (HPLC)

Aculeacin A, an amphophilic antibiotic, inhibits the biosynthesis of β−glucan by selective blockage of β(1→3) glucan synthase.

A7603-1MG

Azaserine, ≥98% (TLC) Azaserine is an antibiotic and antifungal; it may also act as a tumor inducer. It is a structural analog of glutamine and competes with glutamine in binding to enzymes involved in purine biosynthesis. Azaserine inhibits purine biosynthesis by covalently reacting with cysteine residues in the enzyme active sites, such as in formylglycinamide ribonucleotide amidotransferase and PRPP amidotransferase. Azaserine can induce DNA damage via the formation of carboxymethylated bases and O6-methylguanine. Secretion of exo-1,3-β-glucanase and germ-tube formation of Candida albicans were inhibited by azaserine.

A4142-50MGA4142-250MG

Chitin Synthesis InhibitorsName Description Cat. No.

Cycloheximide, BioChemika, ≥93.0% (HPLC) Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors.

01810-1G01810-5G

Cycloheximide, from microbial, ≥94% (TLC) Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors.

C7698-1GC7698-5G

Cycloheximide, Biotechnology Performance Certified

Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors.

C1988-1GC1988-5G

Cycloheximide solution, Ready-Made Solution, microbial, 100 mg/mL in DMSO, 0.2 μm filtered

Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors.

C4859-1ML

Nikkomycin Z from Streptomyces tendae, ≥90% (HPLC)

Nucleoside peptide antibiotic; it inhibits the biosynthesis of chitin in cell walls due to its structural resemblance to UDP-N-acetylglucosamine. Nikkomycin Z has potent antifungal, insecticidal and acaridicial activity.

N8028-5MG




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Interferes with DNA, RNA, or Protein SynthesisName Description Cat. No.

Cordycepin, from Cordyceps militaris Converted to cordycepin 5′-triphosphate. It is incorporated into nucleic acid by poly(A) polymerase, but because it lacks a 3′-hydroxyl group, it causes chain termination. It can be used for 3′-end labeling of RNA.

C3394-10MGC3394-25MGC3394-100MG

5-Fluorocytosine Nucleoside analog that has antifungal activities. 5-FC is deaminated by cytosine deaminase to product 5-fluorouracil, resulting in RNA miscoding. 5-Fluorocytosine inhibits DNA and RNA synthesis and interferes with ribosomal protein synthesis.

F7129-1GF7129-5G

8-Hydroxyquinoline, crystalline RNA synthesis inhibitor that acts as a fungicide against Trichophyton mentagrophytes, Myrothecium verrucaria, and Trichoderma viride. The antifungal mechanism of action is not clear but appears to be structurally related.

H6878-25GH6878-100GH6878-500G

Hygromycin B from Streptomyces hygroscopicus, powder, cell culture tested, insect cell culture tested

Mode of Action: Blocks polypeptide synthesis and inhibits elongation. For use in the selection and maintenance of prokaryotic and eukaryotic cells.

H3274-50MGH3274-100MGH3274-5X100MGH3274-250MGH3274-1G

Hygromycin B from Streptomyces hygroscopicus, lyophilized powder

Mode of Action: Blocks polypeptide synthesis and inhibits elongation. For use in the selection and maintenance of prokaryotic and eukaryotic cells.

H7772-50MGH7772-100MGH7772-250MGH7772-1G

Hygromycin B solution from Streptomyces hygroscopicus, ≥60% (HPAE), 45-60 mg/mL in H2O

Antibacterial and antifungal. Mode of action: Inhibition of protein synthesis, by inducing the misreading of the m-RNA template in prokaryotes and eukaryotes. It selectively penetrates cells that have been rendered permeable by virus infection.

H0654-250MGH0654-500MGH0654-1G

Hygromycin B solution from Streptomyces hygroscopicus, ≥60% (HPAE), 45-60 mg/mL in H2O, γ-irradiated

Antibacterial and antifungal. Mode of action: Inhibition of protein synthesis, by inducing the misreading of the m-RNA template in prokaryotes and eukaryotes. It selectively penetrates cells that have been rendered permeable by virus infection.

H5527-250MGH5527-500MGH5527-1G

Kasugamycin hydrochloride from Streptomyces kasugaensis, ≥90% (HPLC)

Antifungal aminoglycoside. Mode of action: Inhibits protein synthesis and binding of aminoacyl-SRNA to the ribosomes in fungi.

K4013-10G

Phleomycin from Streptomyces verticillus, powder

Phleomycin is a structurally related form of the antibiotic, bleomycin. Phleomycin blocks S-phase entry in the cell cycle. While phleomycin can damage DNA, like bleomycin, it is not used as an anticancer agent, but rather as a selection agent. The RAD6 DNA repair gene is essential for phleomycin resistance in mutant yeast.

P9564-5MGP9564-25MGP9564-100MG

Sordarin sodium salt, from Sordaria araneosa, ≥98% (HPLC), solid

Sordarin is an antifungal metabolite possessing a tetracyclic diterpene glycoside structure. It is a highly potent inhibitor of eukaryotic protein synthesis with selectivity for the fungal translation machinery. The elongation factor eEF-2 is the molecular target for sordarin. It blocks ribosomal translocation by stabilizing the EF2-ribosome complex in a manner similar to that of fusidic acid in the bacterial system. Additional cellular components (including rpP0, which is an essential protein of the ribosomal large subunit stalk) are involved in its mechanism of action. Sordarin inhibits in vitro translation in the pathogenic fungi C. albicans, C. glabrata, and C. neoformans. In addition to its therapeutic potential, sordarin is a useful tool for the analysis of protein translation events.

S1442-5MG

Thiolutin, from Streptomyces luteosporeus, ≥95% (HPLC)

Thiolutin is a sulfur-containing antibiotic, which is a potent inhibitor of bacterial and yeast RNA polymerases. It was found to inhibit in vitro RNA synthesis directed by all three yeast RNA polymerases (I, II, and III). Thiolutin is also an inhibitor of mannan and glucan formation in Saccharomyces cerevisiae and used for the analysis of mRNA stability. Studies have shown that thiolutin inhibits adhesion of human umbilical vein endothelial cells (HUVECs) to vitronectin and thus suppresses tumor cell-induced angiogenesis in vivo.

T3450-1MG

Tubercidin, from Streptomyces tubercidicus, ~95% Toxic adenosine analog with antiviral, antitrypanosomal, and antifungal functions. Mode of action: Inhibits multiple metabolic processes, including RNA processing, nucleic acid synthesis, protein synthesis, and methylation of tRNA through intracellular incorporation into nucleic acids. Tubercidin acts as a plant antifungal, inhibits mammalian SAH hydrolase (SAHH), and blocks purine biosynthesis in Candida famata.

T0642-10MGT0642-50MGT0642-250MG









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Additional Antifungal CompoundsName Description Cat. No.

Amiodarone hydrochloride, ≥98% Non-selective ion channel blocker with broad fungicidal activity. Amiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death.

A8423-1GA8423-5GA8423-10G

Anisomycin from Streptomyces griseolus, ~97% (TLC), solid

Antibiotic isolated from Streptomyces griseolus that inhibits protein synthesis. Acts by inhibiting peptidyl transferase activity in eukaryote ribosomes. Reported to induce apoptosis in a variety of cells including promyelocytic leukemia cells, Jurkat cells, ventricular myocytes, and colon adenocarcinoma cells. Initiates intracellular signals and immediate early gene induction. Selective signaling agonist. Potent Jun-NH2 terminal kinase (JNK) agonist. Activates mitogen-activated protein (MAP) kinases (JNK/SAPK and p38/RK). Antiprotozoal agent.

A9789-5MGA9789-25MGA9789-100MG

Bafilomycin A1 from Streptomyces griseus, ≥90% (HPLC)

A specific inhibitor of vacuolar type H+-ATPase (V-ATPase) in animal cells, plant cells and microorganisms. B1793-2UGB1793-10UG

Cecropin A, ≥97% (HPLC), powder Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. C6830-.1MGC6830-.5MG

Griseofulvin, from Penicillium griseofulvum, 97.0-102.0%

Antifungal. Mode of action: Disrupts the mitotic spindle structure and inhibits nuclear division. Induces apoptosis in human tumor cell lines.

G4753-5GG4753-25GG4753-50G

Irgasan, BioChemika, ≥97.0% (HPLC) Irgasan is a broad spectrum antimicrobial agent. It is an inhibitor of the enoyl-ACP (acyl-carrier protein) reductase component of type II fatty acid synthase (FAS-II) in bacteria and Plasmodium. It also inhibits mammalian fatty acid synthase (FASN), and may have anticarcinogenic activity.

72779-5G-F72779-25G-F

Iturin A from Bacillus subtilis, ≥90% (HPLC) Iturin A exhibits strong antifungal activity against pathogenic yeast and fungi. It interacts with the cytoplasmic membrane of the target cell forming ion conducting pores and its mode of action could be attributed to its interaction with sterols and phospholipids. The compound causes the release of exo-vesicles from human erythrocytes.

I1774-1MGI1774-5MG

Leptomycin B from Streptomyces sp., 5 μg/mL in methanol: water (7:3), ≥95% (HPLC)

Leptomycin B is an unsaturated, branched-chain fatty acid, and is an important tool in the study of nuclear export. It is a specific inhibitor of proteins containing nuclear export signal. It inhibits nucleo-cytoplasmic translocation of molecules such as the HIV-1 Rev protein and Rev-dependent export of mRNA. The addition of very small amounts to fibroblasts causes accumulation of MEK in the nucleus. Other proteins that are influenced by leptomycin B are actin, c-Abl, cyclin B1, MDM2/p53, IκB, MPF, and PKA. The suggested inhibition mechanism involves the direct binding of leptomycin B to CRM1, which blocks the binding of CRM1 to proteins containing the nuclear export signal, via the interaction with cysteine residue in CRM1 control conserved region.

L2913-.5UGL2913-2X.5UGL2913-5X.5UGL2913-10X.5UG

Magnolol, ≥95% (HPLC), from plant 8 Bioactive plant component with antifungal, antibacterial and antioxidant effects. Magnolol also demonstrates anti-inflammatory activity by interferring with NF-κB signaling.

M3445-10MG

Nourseothricin sulfate, BioChemika, ≥85% (HPLC)

Antifungal effective against Candida albicans. Candida species transformed with the gene encoding nourseothricin acetyltransferase (CaNAT1) were resistant to nourseothricin.

74667-10MG

Oligomycin from Streptomyces diastatochromogenes, ~65% oligomycin A basis (Composition given on label), ≥90% total oligomycins basis (HPLC)

Macrolide antibiotic; inhibits mitochondrial ATPase and phosphoryl group transfer. O4876-5MGO4876-25MGO4876-100MGO4876-250MG

Rapamycin from Streptomyces hygroscopicus, ≥95% (HPLC), powder

Rapamycin is a macrocyclic triene antibiotic possessing potent immunosuppressant and anticancer activity. It forms a complex with FKBP12 that binds to and inhibits the molecular target of rapamycin (mTOR). mTOR is a member of the phosphoinositide kinase-related kinase (PIKK) family that enhances cellular proliferation via the phosphoinositol 3-kinase/Akt signaling pathway. Inhibition of this pathway by rapamycin blocks downstream elements that result in cell cycle arrest in G1. The effectors of mTOR action include 4EBP1 and S6K1.

R0395-1MG

Stigmatellin, BioChemika, ≥95.0% (HPLC) Antibiotic and antifungal from Stigmatella aurantiaca. Inhibits electron transport. Acts at the Qo center of the bc1 complex, binds to the heme b1 domain of cytochrome b as well as to the iron-sulfur protein. Used in studies on hydroubiquinone-cytochrome c2 oxidoreductase.

85865-1MG85865-10MG

Surfactin, from Bacillus subtilis, ≥98% Lipopeptide antibiotic; powerful biosurfactant causes lysis of erythrocytes and bacteria; also a clotting inhibitor.

S3523-10MGS3523-50MG

Tunicamycin from Streptomyces sp. Antibacterial and antifungal. Blocks the formation of protein N-glycosidic linkages by inhibiting the transfer of N-acetylglucosamine 1-phosphate to dolichol monophosphate. Inhibits bacterial and eukaryote N-acetylglucosamine transferases and prevents formation of N-acetylglucosamine lipid intermediates.

T7765-1MGT7765-5MGT7765-10MGT7765-50MG


















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New AntibioticsAdefovir dipivoxil 8

9-(2[bis(Pival oyl oxy methoxy)phos phor yl methoxy]ethyl)adenine [142340-99-6] C20H32N5O8P FW 501.47Antiviral acyclic nucleoside phosphonate (ANP) analog. store at: −20°C

A9730-50MG 50 mg

A9730-100MG 100 mg

Artesunate 8

C19H28O8 FW 384.42Artesunate is a semisynthetic derivative of artemisinin used to treat malaria.1 It has also been shown to effective against other parasites such as liver flukes.2 Artesunate also demonstrates cytotoxic action against cancer cell lines of different tumor types.3

Lit cited: 1. Prince, R.N., Expert Opin. Investig. Drugs 9, 1815-1827 (2000); 2. Keiser, J., et. al., Antimicrob. Agents Chemother. 57, 1139-1145 (2006); 3. Efferth, T., et. al., Mol. Pharmacol. 64, 382-394 (2003);

from Artemisia annua store at: Room temp

A3731-100MG 100 mg

A3731-500MG 500 mg

Brefeldin A 8

γ,4-Dihydroxy-2-(6-hydroxy-1-heptenyl)-4-cyclo-pentane croton ic acid λ-lactone; BFA; Cyanein; Ascotoxin; Decumbin

[20350-15-6] C16H24O4 FW 280.36

O

O CH3

HO

H

HO

H

Disrupts the structure and function of the Golgi apparatus; activator of the sphingomyelin cycle.

from Penicillium brefeldianum, Ready Made Solution, 10 mg/mL in DMSO, 0.2 μm filtered

ship: wet ice store at: 2-8°C

B5936-200UL 200 μL

Cefdinir 8

[6R-[6α-7beta(Z)]]-7-[[(2-Amino-4-thia zolyl)(hydroxy imino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-aza bicyclo[4.2.0]oct-2-ene-2-carboxy lic acid; BMY-28488; FK-482; syn-7-[2-(2-amino-4-thia zolyl)-2-hydroxy imino-acet amido]-3-vinyl-3-cephem-4-carboxy lic acid [91832-40-5] C14H13N5O5S2 FW 395.41An advanced-generation, cephalosporin antibiotic. Used for its excellent and well balanced antibacterial activities against gram-positive and gram-negative bacteria.

solidsolubility dilute HCl .............................................................................slightly solublemp ..................................................................................................... 170 °C store at: Room temp

C7118-1G 1 g

C7118-5G 5 g

Clarithromycin 8

[81103-11-9] C38H69NO13 FW 747.95Clarithromycin is a macrolide antibiotic. It prevents bacterial growth by interfering with protein synthesis. Clarithromycin is an acid-stable version of erythromycin and is particularly effective against gram-negative bacteria.1 It has a short half-life2, however its metabolite, 14-hydroxy clarithromycin is nearly twice as active as clarithromycin against certain bacteria.3 Lit cited: 1. Hardy, D.J. et al., Diagn. Microbiol. Infect. Dis. 15, 39-53 (1992); 2. Langtry, H.D., and Brogden, R.N., Drugs 53, 973-1004 (1997); 3. Hardy, D.J, et al., Antimicrob. Agents Chemother. 32, 1710-1719 (1988);

≥95% (HPLC)C9742-100MG 100 mg

C9742-250MG 250 mg

C9742-1G 1 g

Cyto chalasin B from Drechslera dematioidea 8

Phomin

[14930-96-2] C29H37NO5 FW 479.61CH2

O

OHN

O

H

OH

H

OH

H3CCH3

One of a group of fungal metabolites that interfere with a wide variety of cellular movements. Useful tool for characterizing some of the polymerization properties of actin,† and in studies on cytokinesis.1 Probe for the two hexose-transport systems in rat L6 myoblasts.2

Lit cited: 1. S. Eperon, J. Protozool. 33, 43 (1986); 2. S.R.Chen, Biochem. J. 251, 3 (1988);

Ready Made Solution, 10 mg/mL in DMSO, 0.2 μm filteredInhibits actin polymerization; inhibits glucose transport.ship: wet ice store at: −20°C

C2743-200UL 200 μL

Cyto chalasin D 8

Zygosporin A

[22144-77-0] C30H37NO6 FW 507.62

HN

OO

H2C

O

O

OH

HO

H3C

CH3H3C

CH3

H H

H

Potent inhibitor of actin polymerization; disrupts actin microfilaments; activates the p53-dependent pathways; inhibits smooth muscle contraction; inhibits insulin-stimulated glucose transport.

Ready Made Solution, from Zygosporium masonii, 5 mg/mL in DMSO, 0.2 μm filtered

ship: wet ice store at: −20°C

C2618-200UL 200 μL

17-Dimethyl amino ethyl amino-17-de methoxy gel- 8

danamycin17-DMAG C32H48N4O8 FW 616.7517-DMAG is a more potent water soluble analog of geldanamycin. Inhibits cancer growth and promotes apoptosis in multiple cell lines. 17-DMAG is a more potent antitumor agent than 17-AAG.solubility DMSO ...................................................................................... >25 mg/mL ethanol ..................................................................................... ~10 mg/mL store at: −20°C

D5193-1MG 1 mg

Pediocin from Pediococcus acidilactici 8

[133108-87-9]Pediocins are class IIa bacteriocins that are produced by Pediococcus sp.1 They are cationic peptides that show strong activity against pathogenic bacteria such as Listeria monocytogenes, Clostridicum perfringes, Enterococcus faecalis, and Staphylococcus aureus.2 This antimicrobial action of pediocins is based on interaction with the cytoplasmic membrane, resulting in pore formation and cell death.Lit cited: 1. Bauer, R. and Dicks, L.M., Mode of action of lipid II-targeting lantibiotics. Int. J. Food Microbiol. 101, 201-16 (2005); 2. Bhunia, A.K., et al., Purification, characterization and antimicrobial spectrum of a bacteriocin produced by Pediococcus acidilactici. J. Appl. Bacteriol. 65, 261-8 (1988);

≥95% (HPLC), buffered aqueous solutionconcentration ............................ 0.1 mg/mL in 0.1 M sodium acetate pH 5.0ship: dry ice store at: −20°C

P0098-50UG 50 μg



















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Pefloxacin mesylate dihydrate 8

Pefloxaci nium meth ane sulfo nate di hydrate; Pefloxacine mono-meth ane sulfo nate di hydrate; 3-Quino line carboxy lic acid, 1-ethyl-6-fluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-, mono meth ane-sulfo nate, di hydrate

C17H20FN3O3 • CH4O3S • 2H2O

FW 465.49

N

O

H3C

F

NN

H3C

O

OH SO

OCH3HO•

• 2H2O

Pefloxacin is a synthetic fluoroquinolone that functions an antibacterial agent. It is an analog of norfloxacin.

Mode of Action: Pefloxacin prevents bacterial DNA replication by inhibiting DNA gyrase.

Antimicrobial spectrum: Pefloxacin is highly active against Staphylococcus aureus, E. coli, other enterobacteria, and Pseudomonas aeruginosa.1 Active against gram-positive bacteria and excellent activity against gram-negative bacteria.2

Lit cited: 1. Jones, B.M. et al., Activity of pefloxacin and thirteen other antimicrobial agents in vitro against isolates from hospital and genitourinary infections J. Antimicrob. Chemother. 17, 739-746 (1986); 2. Debbia, E. et al., In vitro activity of pefloxacin against gram-negative and gram-positive bacteria in comparison with other antibiotics. Chemotherapia 6, 319-326 (1987); store at: 2-8°C

P0106-10G 10 g

P0106-50G 50 g

Peni cil lic acid 8

3-Methoxy-5-methyl-4-oxo-2,5-hexa dienoic acid; PA [90-65-3] C8H10O4 FW 170.16Penicillic acid is a polyketide mycotoxin produced by several species of Aspergillus and Penicillium species. It induces single and double strand DNA breaks. Penicillic acid irreversibly inhibits GDP-mannose dehydrogenase (DMG), an alginate synthesis enzyme. It also inhibits muscle aldose dehydrogenase, alcohol dehydrogenase, and lactate dehydrogenase.

≥98% (HPLC)solubility H2O ...........................................................................................≤10 mg/mL DMSO ...................................................................................... >10 mg/mL store at: 2-8°C

P0063-10MG 10 mg

P0063-50MG 50 mg

Pirarubicin 8

THP

[72496-41-4] C32H37NO12 FW 627.64O

OCH3O

OH

OH

OHO

OH

OO

CH3

NH2

OO

Anthracycline antibiotic that is an analog of doxorubicin. Antineoplastic. Pirarubicin is transported into cells vial a sodium-dependent nucleoside transporter.1,2

Lit cited: 1. Nagai, K., et al., Pirarubicin is taken up by a uridine-transportable sodium-dependent concentrative nucleoside transporter in Ehrlich ascites carcinoma cells. Cancer Chemother. Pharmacol. 51, 512-8 (2003); 2. Nagai, K., et al., Uptake of the anthracycline pirarubicin into mouse M5076 ovarian sarcoma cells via a sodium-dependent nucleoside transport system. Cancer Chemother. Pharmacol. 55, 222-30 (2005);

≥95% (HPLC)ship: wet ice store at: 2-8°C

P8624-10MG 10 mg

P8624-25MG 25 mg

Rapamycin 8

23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxa aza cyclo hen tria contine solution C51H79NO13 FW 914.17Rapamycin is a macrocyclic triene antibiotic possessing potent immunosuppressant and anticancer activity. It forms a complex with FKBP12 that binds to and inhibits the molecular target of rapamycin (mTOR). mTOR is a member of the phosphoinositide kinase-related kinase (PIKK) family that enhances cellular proliferation via the phosphoinositol 3-kinase/Akt signaling pathway. Inhibition of this pathway by rapamycin blocks downstream elements that result in cell cycle arrest in G1. The effectors of mTOR action include 4EBP1 and S6K1.

Ready Made Solution, 2.5 mg/mL in DMSO (2.74 mM), from Streptomyces hygroscopicus

≥95% (HPLC)

0.2 μm filtered store at: −20°C

R8781-200UL 200 μL

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Rifaximin 8

Rifacol; 4-Deoxy-4′-methyl pyrido[1′,2′-1,2]imidazo[5,4-c]rifamycin SV

[80621-81-4] C43H51N3O11 FW 785.88

O

NH

O O

O

O

OHOH

OH

OH

O

O NN

CH3

Rifaximin is a semisynthetic analog of rifamycin with poor absorptivity. Mode of action: Inhibition of RNA synthesis.

Antimicrobial spectrum: Aerobic and anaerobic Gram-positive and Gram-negative bacteria. Active against species of Staphylococcus, Streptococcus and Enterococcus; less active against species of Enterobacteriaceae.1

Lit cited: 1. Gillis, J.C. and Brogden, R.N., Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs 49, 467-84 (1995); store at: 2-8°C

R9904-1G 1 g

R9904-5G 5 g

Spiramycin adipate 8

Spiramycin hexane dioate

Macrolide antibiotic

Mode of action: Interferes with protein synthesis

Antimicrobial spectrum: mainly Gram-positive bacteria store at: 2-8°C

S3072-1G 1 g

S3072-5G 5 g

Sulfa doxin 8

[2447-57-6] C12H14N4O4S FW 310.33

N

N

HNS

O O

H3CO

H3CO

NH2

≥95% (TLC)Sulfadoxine is a sulfonamide antibacterial. It inhibits dihydropteroate synthase (DHPS), an enzyme that transforms 4-aminobenzoic acid (PABA) in the synthesis of dihydropteroic acid. This enzyme is also a component of the folate metabolic pathway and is upstream of dihydrofolate reductase (DHFR). Sulfadoxine has been used clinically in combination with pyrimethamine for malaria treatment.

S7821-10G 10 g

S7821-25G 25 g

Terbinafine hydrochloride 8

trans-N-(6,6-Dimethyl-2-hepten-4-ylyl)-N-methyl-1-naph thyl methyl amine hydrochloride

[78628-80-5] C21H25N · HCl FW 327.89

NCH3 H

HCH3

CH3CH3

• HCl

Mode of Action: Inhibits squalene epoxidase, preventing biosynthesis of ergosterol.

Antimicrobial spectrum: Antifungal and antimycotic. Fungicidal against dermatopytes and some yeasts; fungistatic against Candida albicans.

Allylamine derivative.

≥98%T8826-100MG 100 mg

T8826-250MG 250 mg

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Ready Made SolutionsSigma® Life Science Antibiotic Ready Made Solutions arrive at your laboratory as sterile-filtered, ready to use formulations. Ready Made antibiotic solutions minimize your exposure to potentially harmful powders, reducing your risk as well as saving your time. All Ready Made Solutions are 0.2 μm filtered for extended shelf life and prevention of bacterial contamination. As with all Sigma Life Science products, strict quality control measures apply to each Ready Made Solution. For more information on Ready Made Solutions, please visit sigma.com/readymade

Name Concentration Source Description Cat. No.

Ampicillin 100 mg/mL microbial A β-lactam antibiotic with an amino group side chain attached to the penicillin structure. Penicillin derivative that inhibits bacterial cell-wall synthesis (peptidoglycan cross-linking) by inactivating transpeptidases on the inner surface of the bacterial cell membrane. Bactericidal only to growing Escherichia coli. Mode of resistance: Cleavage of β-lactam ring of ampicillin by β-lactamase. Antimicrobial spectrum: Gram-negative and Gram-positive bacteria.

A5354-10ML

Brefeldin A 8 10 mg/mL in DMSO Penicillium brefeldianum

Disrupts the structure and function of the Golgi apparatus; activator of the sphingomyelin cycle.

B5936-200UL

Carbenicillin 100 mg/mL in ethanol/water

- The antibiotic carbenicillin, an ampicillin analog, is a commonly used selection agent that binds and inhibits enzymes involved in the synthesis of the bacterial cell wall. It is active against most isolates of Pseudomonas aerogenosa and certain indole-positive Proteus strains that are resistant to ampicillin. The gene conferring resistance to ampicillin and its analogs, ampr, codes for the enzyme β-lactamase. Carbenicillin is less sensitive to β-lactamase than ampicillin. In addition it has a superior stability at low pH. Experiments have shown that the use of carbenicillin in place of ampicillin helps prevent overgrowth of satellite colonies. Effective concentration: 50 to 100 μg/ml.

C1613-1ML

Cycloheximide solution 100 mg/mL in DMSO

microbial Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors.

C4859-1ML

Cytochalasin B from Drechslera dematioidea 8

10 mg/mL in DMSO Drechslera dematioidea

One of a group of fungal metabolites that interfere with a wide variety of cellular movements. Useful tool for characterizing some of the polymerization properties of actin,† and in studies on cytokinesis. Probe for the two hexose-transport systems in rat L6 myoblasts.Inhibits actin polymerization; inhibits glucose transport.

C2743-200UL

Cytochalasin D 8 5 mg/mL in DMSO Zygosporium masonii

Potent inhibitor of actin polymerization; disrupts actin microfilaments; activates the p53-dependent pathways; inhibits smooth muscle contraction; inhibits insulin-stimulated glucose transport.

C2618-200UL

Ionomycin calcium salt 1 mM in DMSO Streptomyces conglobatus

Ca2+ ionophore that is more effective than A23187 as a mobile ion carrier for Ca2+.

I3909-1ML

Puromycin dihydrochloride 10 mg/mL in H2O Streptomyces alboniger

Puromycin inhibits the growth of a wide range of eukaryotic and prokaryotic cells by interfering with protein synthesis. It allows the selection of cells expressing the pac gene.

P9620-10ML

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Name Concentration Source Description Cat. No.

Rapamycin 8 2.5 mg/mL in DMSO (2.74 mM)

Streptomyces hygroscopicus

Rapamycin is a macrocyclic triene antibiotic possessing potent immunosuppressant and anticancer activity. It forms a complex with FKBP12 that binds to and inhibits the molecular target of rapamycin (mTOR). mTOR is a member of the phosphoinositide kinase-related kinase (PIKK) family that enhances cellular proliferation via the phosphoinositol 3-kinase/Akt signaling pathway. Inhibition of this pathway by rapamycin blocks downstream elements that result in cell cycle arrest in G1. The effectors of mTOR action include 4EBP1 and S6K1.

R8781-200UL

Spectinomycin 100 mg/mL in DMSO/H2O, 1:1

Streptomyces sp. Mode of Action: Inhibits protein synthesis (elongation) by interfering with peptidyl tRNA translocation. Antimicrobial spectrum: Gram-negative and Gram-positive bacteria (Gonnococcus only).Mode of Resistance: Mutation in rpsE (the gene for ribosomal protein S5) prevents binding of spectinomycin.Broad spectrum antibiotic produced by the soil bacterium Streptomyces spectabilis. Spectinomycin inhibits protein synthesis (elongation) by binding to the bacterial 30S ribosomal subunit and interfering with peptidyl tRNA translocation. Resistance to spectinomycin is conferred by aminoglycoside-3′-adenyltransferase gene (aadA).Spectinomycin is used as a selection marker in plant related transformation systems. Spectinomycin is also used for amplification of low copy number plasmid carrying replicons as Col E1, pMB1 (pBR322 and its derivatives), and p15A/rep (pACYC and its derivatives). The replication of these plasmids relies on long-lived enzymes supplied by the host. Addition of spectinomycin to the plasmid containing cells inhibits replication of the host, while the plasmids continue to replicate for 10-15 hours. The copy number of the plasmid can increase 100-fold, from 20-30 copies to 3000 copies as in the case of ColE1.

S0692-1ML

Staurosporine solution from Streptomyces sp.

1 mM in DMSO (100 μg/214 μL)

Streptomyces sp. Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells.Potent cell-permeable inhibitor of protein kinase C. Induces apoptosis in Jurkat cells.

S6942-200UL

Trichostatin A 8 5 mM in DMSO (0.2 μm-filtered)

Streptomyces sp. Trichostatin A is a Streptomyces metabolite, which specifically inhibits mammalian histone deacetylase.

T1952-200UL

Valinomycin ~ 1 mg/mL in DMSO Streptomyces sp. K+-selective ionophore which uncouples oxidative phosphorylation. V3639-5ML

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The 3rd edition of the Sigma Cell Culture Manual is a hybrid reference and product guide designed to be a foundation for your discovery efforts.

■ Extensive cell culture technical information and formulas

■ Our most popular cell culture products and equipment

■ Invaluable tool to help advance your research goals

Order your copy of the 2008–2009 Cell Culture Manual by visiting sigma.com/ccmanual

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Antibiotic Selector■ Quickly find the best antibiotic for your research.

■ Detailed application and usage information.

■ Link to easy online ordering.

The Antibiotic Selector enables researchers to spend more time on their research discoveries and less time seeking established antibiotic information. Link to nearly 200 antibiotics for contamination prevention, genetic marker selection and cell biology studies. Access application, activity spectrum, and usage data derived from a combination of hands on experience, peer-reviewed literature, and Sigma quality control analysis.

For more information, visit sigma.com/antibiotics

Search-

If you already know your antibiotic of interest, search the name then select it from the results to access the detailed usage and application information.

Close the window to return to the main antibiotic selector window. Start a new search by clicking the red “New Search” button.

The following tutorial provides instructions on how to:

■ Search, browse and filter for an antibiotic that meets your research requirements

■ Access solvent, solution storage and working concentration recommendations for each antibiotic

■ Link to current pricing, availability and easy, online ordering

Search by antibiotic name

Application and usage information


We expect the Antibiotic Selector to be a beneficial tool for you and your colleagues, however we do have an alternative antibiotic resource available to you. An Antibiotic Selection Poster has been created with the same application, usage and product number information. To request this poster or access the Antibiotic Selector, please visit sigma.com/antibiotics

Browse-

To browse antibiotics by application, select one of the following from the Application menu: cell culture, plant cell culture, selection agent, antineoplastic agent.

To browse antibiotics by activity spectrum, select one of the following from the Activity Spectrum menu: Gram +, Gram -, Mycobacteria, Yeast, Molds, Mycoplasmas and Viruses.

You can further refine your results by first browsing the antibiotics by application and then filtering the results by a specific activity spectrum or first browsing by activity spectrum and then filtering the results by application. Click on your antibiotic of interest from the list to access the detailed usage information.

Once you have completed a search, be sure to start a new search by clicking the red “New Search” button before starting a new search or browsing by application or activity spectrum.

Online Ordering-

The Antibiotic Selector links to an online ordering page for each antibiotic product. The online ordering page displays current pricing and availability information.

Browse by activity spectrum

Browse by application

Price and availability


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The Bioactive Nutrient ExplorerYour connection to plant defense compounds

Designed to help you locate the chemicals and kits needed to support your antimicrobial-

related phytochemical research, the Bioactive Nutrient Explorer is an Internet-based tool

that identifies the compounds found in a specific plant and arranges them by chemical

family and class. You can also search for compounds having a similar chemical structure or

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simple mouse click links you to our easy online ordering system.

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