effect of the side group on the helix-forming tendency of α-alkyl-β-l-aspartamyl residues

Carlos Aleman,Juan J. Navas, Effect of the Side Group onSebastian Munoz-Guerra

Departament d’Enginyeria the Helix-Forming TendencyQuimica, of a-Alkyl-b-L-AspartamylETS d’Enginyers Industrials de

Barcelona, ResiduesUniversitat Politecnica de

Catalunya,Diagonal 647,

Barcelona E-08028, Spain

Received 21 June 1996;accepted 4 October 1996

Abstract: The conformational preferences of the monomeric units of a series of poly(a-alkyl-b-L-aspartate)s were examined by quantum mechanical calculations. a-Alkyl-b-aspartamyl m-oligopeptides with a number of residues m ranging from 1 to 7 and arranged in the conforma-tions experimentally observed for their corresponding polymers were computed. Both theirtotal relative energies and their cooperative energy differences were compared as a functionof the length of the oligopeptide and the nature of the alkyl side group. Results revealed thatthe 13/4 helical arrangement is the most stable structure for the isolated polymer chain forany side group, although a 17/4 helix becomes favored in the case of methyl and ethyl groupsdue to the packing effects. On the other hand, the stability of the 4/1 helix appears to be thepreferred conformation for side groups with a branched constitution. q 1997 John Wiley &Sons, Inc. Biopoly 41: 721–729, 1997

Keywords: Poly(b-L-aspartate)s; helical conformations; quantum mechanical calculations;cooperative energy effects; helix stability

INTRODUCTION for their ability to display a-helix-like conforma-tions.3–11 A schematic representation of the generalstructural formula of these polymers with specifica-One of the aims of the contemporary research intion of the members that have been examined sopolymers is the rational design of synthetic com-far is depicted in Figure 1.pounds made of structural motifs similar to those

Different helical arrangements and modes offound in naturals.1,2 An attractive approach to thispacking have been found for these compounds de-aim is to devise nonpolypeptidic polyamides ablepending on the constitution of the alkyl side group.to adopt helical structures of the type found in pro-Furthermore, more than one helical form are some-teins. In particular, we are interested in poly(b-L-times adopted by the same compound. A summaryaspartate)s, a family of stereoregular poly(b-am-

ide)s extensively investigated during the last decade of the different helical conformations and crystal

Correspondence to: Carlos AlemanContract grant sponsor: DGICYTContract grant number: PB93-0960

q 1997 John Wiley & Sons, Inc. CCC 0006-3525/97/070721-09

721

5417/ 8k1f$$5417 03-18-97 19:47:06 bpa W: Biopolymers

722 Aleman, Navas, and Munoz-Guerra

containing from 3 to 22 carbon atoms (PAALA-3to PAALA-22) as well as for the isobutyl(PAIBLA) and the 2-methoxyethyl (PAMELA) de-rivatives. The second helical arrangement in impor-tance adopted by these polymers consists of a right-handed 4/1 helix with hydrogen bonds linkingresidues i and i / 4. The occurrence of this confor-mation is restricted to the solid state of those mem-bers bearing alkyl side chains with lengths between2 and 5 carbon atoms. Finally, a right-handed 17/4 helix with a hydrogen-bonding scheme similar tothat present in the 4/1 helix, has been put forwardfor PAALA-1 and PAALA-2. In summary, threetypes of helices—13/4, 17/4, and 4/1—with hy-drogen bonds arranged in either of two schemes—namely i 0 i / 3 and i 0 i / 4—are known forpoly(b-L-aspartate)s up to date.

The constitution of the side chain is also determi-nant of the degree of order and type of geometry

FIGURE 1. General formula of poly(a-alkyl-b-L-aspar-displayed by poly(b-L-aspartate)s in the solid state.tate)s: PAALA-1, poly(a-methyl-b-L-aspartate); PAALA-The 17/4 helices of PAALA-1 and PAALA-2 as2, poly(a-ethyl-b-L-aspartate); PAALA-n, poly(a-n-alkyl-well as 13/4 helices of members with short andb-L-aspartate); PAMELA, poly[a-(methoxy-2-ethyl)-b-L-medium alkyl side groups (less than five carbonaspartate); and PAIBLA, poly(a-isobutyl-b-L-aspartate).

Dihedral angle notation is also schematically represented. atoms) crystallize in a pseudohexagonal latticemade of up and down chains. Conversely, 4/1 heli-ces crystallize in a tetragonal lattice with all thechains pointing to the same direction. Both forms,forms found for this family of polyamides is givenpseudohexagonal and tetragonal, are tridimensionalin Table I.molecular arrays with side chains and main-chainThe conformations most frequently observedhelices forming part of the same crystal lattice. Onamong poly(b-L-aspartate)s corresponds to thethe other hand, the packing of 13/4 helices ofright-handed 13/4 helix with hydrogen bonds setpoly(b-L-aspartate)s bearing long linear alkylbetween residues i and i / 3. This helix has been

observed for members with linear alkyl side chains groups is hampered by difficulties arising from the

Table I Selected Structural Data for poly(b-L-Aspartate)s Studied in This Work

HelixPolyamide Side Chain Crystal Form Symmetry H-Bond Scheme Ref.

PAALA-1 Methyl Hexagonal 17/4 i 0 i / 4 10PAALA-2 Ethyl Hexagonal 17/4 i 0 i / 4 10

Tetragonal 4/1 i 0 i / 4 10PAALA-3 n-Propyl Hexagonal 13/4 i 0 i / 3 10

Tetragonal 4/1 i 0 i / 4 10PAALA-4 n-Butyl Hexagonal 13/4 i 0 i / 3 8, 9

Tetragonal 4/1 i 0 i / 4 8, 9PAMELA 2-Methoxyethyl Hexagonal 13/4 i 0 i / 3 9PAIBLA Isobutyl Hexagonal 13/4 i 0 i / 3 7

Tetragonal 4/1 i 0 i / 4 7PAALA-6 n-Hexyl Not crystallized 13/4 i 0 i / 3 6, 11PAALA-8 n-Octyl Rhombic 13/4 i 0 i / 3 6, 11PAALA-n(n Å 8, 12, 18, 22) n-Alkyl Biphasic 13/4 i 0 i / 3 6


Helix-Forming Tendency 723

accommodation of the side chains in the lattice.PAALA-12, -18, and -22 form biphasic structureswith 13/4 helices arranged side-by-side in layersand side chains crystallized in a paraffinic phasefilling the interlayer space. On the other hand,PAALA-6 and PAALA-8 tend to be arranged in asort of mesophase with the helices aligned alongthe molecular axis and the alkyl side groups re-maining in a molten state. However, PAALA-8 isunique in crystallizing by annealing in a tridimen-sional lattice of the type adopted by members withshort alkyl side chains; in this case, however, the13/4 helices are arranged in layers like those oc-curring for the higher members.

The variety of helical conformations found inpoly(b-L-aspartate)s is only matched by that ob-

FIGURE 2. Hydrogen-bonding schemes of the 17/4,served in certain polypeptides like poly(a-L-aspar-4/1, and 13/4 helices of poly(b-L-aspartate)s and theirtate)s and poly(a-L-glutamate)s, to which they areconformational parameters

closely related. As it was done years ago for poly-peptides,12 it would be very interesting to comparethe different alkyl side groups in terms of their abil-

and molecular modeling studies of the respective poly-ity to stabilize the two hydrogen-bonding schemesmers.7–11 The backbone dihedral angles f, j, c, and vfound in poly(b-L-aspartate)s. This knowledge(see Figure 1) of the 17/4, 4/1, and 13/4 helices werewould be of help in understanding the complextaken thereof, where these parameters were stereochemi-structural behavior displayed by these polymers andcally refined against x-ray diffraction data. More specifi-to explain some striking observations like the con-cally, backbone dihedral angles were refined against x-ray

formational transitions from 13/4 to 4/1 helices intensities taking into account the side-chain geometry sotaking place in solid PAIBLA by effect of heating. that interatomic contacts could be minimized simultane-Furthermore, the evaluation of the different energy ously. In such structures hydrogen bonds are almost linearterms will be useful to discern between processes with parameters oscillating within the following ranges:associated to the conformational preferences of the d(HrrrO) Å 1.8–1.9 A, d(NrrrO) Å 2.8–2.9 A, and

õ N{HrrrO Å 1727–1787. Although no helices withisolated chain and those being due to favorablethe i 0 i / 3 hydrogen-bonding scheme were found forpacking interactions.PAALA-1 and PAALA-2, 13/4 helices were also com-Quantum mechanical calculations will be theputed for these polymers for the sake of comparison.method of choice in this work to characterize theThe same was applied for the hypothetical 4/1 helix ofintrinsic helix-forming tendency of poly(b-L-aspar-PAMELA. Figure 2 displays the hydrogen-bond schemestate)s. This theoretical investigation comprises twoand backbone dihedral angles for the three types of heli-

levels of study. First, we examine the relative stabil- ces considered in this work.ity of the different types of helices in connection The calculations were performed using the AM114

with the constitution of the alkyl side group. Sec- semiempirical quantum mechanical method. This is aond, the energy effects arising from cooperative in- well-known method that provides an acceptable descrip-teractions are estimated by using an approach pre- tion of both molecular geometries and hydrogen-bonding

interactions.14–16 Furthermore, the reliability of the rela-viously developed by us.13

tive energies between helical conformations obtained atthe AM1 level was recently proved by comparison withthose computed at the ab initio level using a medium-

COMPUTATIONAL METHODS size basis set.17,18 It was found that the two computationalmethods give the same energy orders, although the AM1relative energies were underestimated with respect to theTo address this study, the relative stabilities of the helical

conformations of a-alkyl-b-L-aspartamyl oligopeptides ab initio ones. Although molecular geometries were mini-mized, the backbone dihedral angles were held fixed atwith a number of residues m varying from 1 to 7 were

computed. Such calculations were performed for the mo- the values displayed in Figure 2 in order to avoid distor-tions of the helical symmetry. All the chains were blockednomeric residues of PAALA-1 to PAALA-4, PAMELA

and PAIBLA. The conformations considered for each res- at the ends with an acetyl and N-methylamide groups,abbreviated Ac and NMe, respectively. The use of elec-idue were those inferred from previous x-ray diffraction



tronic methods permit to investigate the cooperative en- Figure 3. Note that in spite of the similarities ex-ergy effects associated to the generation of a repetitive isting between the conformational parameters of thechemical structure. These effects were computed ac- 17/4 and 4/1 helices (see Figure 2), their projec-cording to the procedure developed in previous tions are clearly different. The two helical arrange-works.13,17,18 Thus, for a given residue X the difference ments i 0 i / 4 and i 0 i / 3 involved in thisbetween the AM1 vacuum heats of formation of the

helices were energetically compared for six differ-blocked dipeptide (AcXNMe) and the tripeptide (AcX2-ent compounds. More specifically, the 17/4 ( i 0 iNMe) in a given conformation can be associated with/ 4) helix was computed for PAALA-1 andthe energy increment (EI) that results when a single resi-PAALA-2; the 4/1 ( i 0 i / 4) helix for PAALA-due is added to the peptide chain with the same conforma-3, PAALA-4, PAMELA, and PAIBLA; and the 13/tion:4 ( i 0 i / 3) helix for all six poly(b-L-aspartate)s.Oligopeptides containing from 1 to 7 monomeric

EI Å DHAM1f (AcXNMe) 0 DHAM1

f (AcX2NMe) (1) units, were computed for each compound.Figure 4 shows the variation of the difference in

conformational energy between i 0 i / 4 and i 0 iThen, the predicted heat of formation for the m-oligopep-/ 3 helices with m , for the six compounds undertide AcXmNMe in such a conformation could be calcu-investigation. In the all six cases, the i 0 i / 3lated fromarrangement was found to be the favored conforma-tion regardless the number of residues contained in

DH predf (AcXmNMe) Å (m 0 1)*EI

(2) the oligopeptide. Moreover, the chemical nature ofthe side chain starts to have a significant influence/ DHAM1

f (AcXNMe)on the relative stability of the two types of arrange-ments only when m is greater than 3. With regardto compounds bearing linear alkyl side chains, theIf the total energy for a defined conformation is devoidenergy difference decreases when the number ofof any cooperative effect, DH pred

f and DHAM1f for AcXm-

NMe must have the same value. Thus, the cooperative methylenes increases. Thus, the stability of i 0 ienergy difference (CED) of a m-oligopeptide is given by / 3 helices over i 0 i / 4 helices varies accordingEq. (3) . Note that the CED must be negative when a to the following order: PAALA-4 õ PAALA-3given conformation is favored for a residue X. In this õ PAALA-2 É PAALA-1. This result is consistentcase the CED will enable us to explain the stabilization with previous molecular mechanics calculationsof such conformation when the number of residues in the carried out for an infinite chain of PAALA-4, whichpolypeptide increases.

revealed that the 13/4 and 4/1 helices are almostisoenergetic.9

The trend observed for the relative energies ofCED (AcXmNMe) Å DHAM1f (AcXmNMe)

(3) PAALA-n in Figure 4 is probably due to the exis-0 DH pred

f (AcXmNMe) tence of favorable van der Waals interactions takingplace in i 0 i / 4 helices, which are predicted tobe weaker as the size of the alkyl groups decreases.

All the calculations were performed with the MOPACThis is in apparent disagreement with previous mod-computer program19 using the AM1 standard parame-eling results which showed that the i 0 i / 4 ar-ters.14 Calculations were run on a CONVEX C3480 atrangement is the preferred one by PAALA-1 andthe Centre Europeu de Paralrlelisme de BarcelonaPAALA-2. However, it should be noted that these(CEPBA).polymers generate 17/4 helices instead of 4/1 heli-ces. As a result, they do not crystallize into the usualtetragonal form but in a less compact hexagonallattice similar to that adopted by the 13/4 helices.RESULTS AND DISCUSSIONSuch striking features suggest that the hexagonalform of the methyl and ethyl derivatives achievesthe lowest free-energy minimum with the i 0 i / 4Side-Chain-Dependent Stability of thescheme in spite that the present calculations indicate17/4, 4/1, and 13/4 Helixthat the 13/4 helix is the favored conformation forConformationsan isolated polymer chain. Therefore we interpretthe conformational behavior of these members toThe axial projections of the three types of helices

observed in poly(b-L-aspartate)s are compared in be due to the contribution of the favorable packing



FIGURE 3. Axial projection of the 17/4, 4/1, and 13/4 helices of poly(b-L-aspartate)s.

interactions. In this regard, it should be noticed that, the former has a diameter about 0.8 A larger thanthe latter. This implies the existence of a largeralthough the 17/4 helix is in axial projection similar

to the 13/4 helix (see Figure 3), they differ in that central hole that disfavors the structure from an en-

FIGURE 4. Variation of the relative energy (in kcal/mol) between helices with schemes i0 i / 4 (17/4 helix for PAALA-1 and PAALA-2; 4/1 helix for PAALA-3, PAALA-4,PAMELA, and PAIBLA) and i0 i/ 3 (13/4 helix) with the number of a-alkyl-b-L-aspartamylresidues. In each case the relative energy was computed as the energy difference with respectto the lowest energy structure.



FIGURE 5. Equatorial projection of the 4/1 helix of PAALA-4 (a) and PAMELA (b) aftergeometry optimization. One of the dihedral angles of the side chain in PAMELA changes from1807 to Ç 1007 due to the electrostatic repulsion between the oxygen atoms of the side groups.

tropic point of view but permits to attain a packing pared. However, results for PAIBLA are fully con-sistent with experimental observations and readilyof the side chains more efficient than in the case of

the 13/4 helix. explainable in terms of the favorable van der Waalsinteractions occurring between the branched sideThe results obtained for PAMELA and PAIBLA

indicate that the preference for the i0 i/ 3 arrange- groups of residues i and i / 4. It is worthy to notethat side-chain interactions in PAIBLA are morement tends to diminish when the number of residues

exceeds 5. This is a surprising result for the case of favorable than in PANBLA due to the branchednature of the side group. A similar situation hasPAMELA since the tetragonal form has not been

experimentally observed for this polymer. A de- been reported for poly(a-amino acid)s with an inte-gral helix symmetry, as it is the case of the 3/1tailed inspection of the 4/1 helix obtained for the

5-, 6-, and 7-oligopeptides reveals that repulsive helix of both poly(a-aminoisobutyric acid)21 andpoly(dehydroalanine) .17,22interactions between the polar oxygen atoms on res-

idues i and i / 4 cause a drastic change in theconformation of the side chains; specifically, one of Influence of the Alkyl Side Groups onthe dihedral angles deviates from 1807 to about the Cooperative Energy Effects1007. In order to ensure that the electrostatic repul-sions between polar oxygen atoms are the responsi- The tendency displayed by the different a-alkyl-b-

L-aspartamyl residues to adopt helical conforma-ble of such conformational change, empirical calcu-lations using the AMBER20 force field were per- tions can be evaluated in terms of cooperative en-

ergy effects. For this purpose the CEDs were ob-formed on the 13/4 and 4/1 helices. The analysisof the different energy terms reveals that the electro- tained following the procedure described in the

methods section. Accordingly, the CEDs [Eq. (3)]static contribution is less favored for the 4/1 helixthan for the 13/4 helix by 1.2 kcal/mol∗residue, were estimated as the difference between the pre-

dicted and the quantum mechanical enthalpies, thewhereas differences in the other energy contribu-tions, i.e., bonding and van der Waals terms, are former being computed by Eq. (2) . Results obtained

for oligomers with seven residues are given in Tablelower than 0.4 kcal/mol∗residue. As a conse-quence, the all-trans conformation characteristic of II. Note that a favorable CED was found in all cases

for both types of helices, indicating that a-alkyl-b-the side chain of poly(b-L-aspartate)s in the tetrag-onal form is severely distorted. Such effect becomes L-aspartamyl residues have a large intrinsic ten-

dency to adopt helical conformations. Such a favor-clearly illustrated in Figure 5 where the equatorialprojections of PAMELA and PANBLA are com- able contribution permits us to predict a greater for



Table II CED (in kcal/mol) in the 7-Oligopeptides nmr studies indicated that poly(b-L-aspartate)s re-of the a-alkyl-b-L-Aspartamyl Residues Investigated tain the helical conformation in solution,3 althoughin the Present Work it was difficult to discern by such means which one

of the two bonding schemes was present in the liq-i 0 i / 3 i 0 i / 4 uid state. On the other hand, it is known that the

favored conformation for polypeptides in solutionPAALA-1 019.5 019.8is that entailing the highest dipole moment.17,23 ThePAALA-2 021.7 021.8general effect of the solvent is to enhance the polar-PAALA-3 022.0 021.4ity of the molecules with the subsequent increasePAALA-4 021.9 022.0of the solvent–polymer interactions. Our results in-PAMELAa 023.8 —

PAIBLA 021.1 022.4 dicate also that the difference between the dipolemoments of the helices i 0 i / 3 and i 0 i / 4

a Cooperative energy difference for the 4/1 helix of PAMELA increases with the number of residues as expectedwas not computed since the structure was not retained after ge-

from the higher stabilization of the former in theometry optimization.solvent phase.

An additional feature worthy to note is that theCDMD decreases as the size of the linear sidegroups increases. Thus, for side groups with a num-the helix when the number of residues increases. A

similar behavior has been recently described for ber of methylene groups large enough the CDMDsof the two types of helical structures would be veryother residues with a proved tendency to take up

helical conformation like L-alanine,13 a-aminoiso- similar. On the other hand, both parameters arelarger for branched side groups than for linear sidebutyric acid,13 and dehydroalanine.17,18

A comparison between helices with hydrogen- groups. The large CDMD of PAIBLA suggest thatthe 13/4 helix should be the most stable conforma-bonding schemes i 0 i / 3 and i 0 i / 4 for

PAALA-1 and PAALA-2 reveals that the energy tion in solution, whereas the 4/1 helix is the moststable conformation in both gas-phase and crystaldifference between the two arrangements is lower

than 0.3 kcal/mol. Such a small value accounts for environment.the fact that packing effects play a decisive rolein the stabilization of the 17/4 helix. Regarding

Extension to Poly(b-L-Aspartate)s withPAALA-3, PAALA-4, and PAIBLA, the CED dif-Long Linear Alkyl Side Groupsference between the two arrangements changes with

the size of the alkyl side group. Thus, for PAALA- As was stated in the introduction section, poly(b-3 the CED of the 13/4 helix is 0.7 kcal/mol larger

L-aspartate)s with long linear alkyl side groups, i.e.,than that of the 4/1 helix, whereas for PAALA-4 PAALA-n with n ¢ 6, display a structural behaviorthe two structures present almost the same CED.These results agree with reported experimental dataaccording to which the conformational transition

Table III SCF Dipole Moments (m in Debyes) andbetween the 13/4 and 4/1 helices is hardly observedCDMD (in Debyes) in the 7-Oligopeptides of the a-in these polymers. Conversely, PAIBLA has a lowerAlkyl-b-L-Aspartamyl Residues Investigated in theCED for the 13/4 helix than for the 4/1 helix, whichPresent Workis in agreement with the 13/4 r 4/1 transition ob-

served in this polymer when subjected to heating.i 0 i / 3 i 0 i / 4

The CED for PAMELA in the i0 i/ 4 arrangementhas not been computed since as we stated in the m CDMD m CDMDprevious section, a nonregular structure was ob-tained in this case. PAALA-1 21.25 05.20 18.73 00.59

PAALA-2 19.02 03.04 18.35 01.51Table III shows the self consistent force (SCF)PAALA-3 18.67 02.73 18.12 00.96dipole moments computed for the 7-oligopeptidesPAALA-4 18.50 02.64 17.89 00.63of helices with schemes i 0 i / 3 and i 0 i / 4 asPAMELAa 13.14 01.17 — —well as their cooperative dipole moment differencesPAIBLA 19.73 03.22 18.01 00.77(CDMD). Note that both magnitudes are always

larger for helices with the i 0 i / 3 scheme, which a SCF dipole moment and CDMD for the 4/1 helix of PA-means that the 13/4 helix will be favored in solution MELA were not computed since this structure was not retained

after geometry optimization.with respect to either 17/4 or 4/1 helices. Previous



clearly different from those with small and medium sible for the stabilization of the latter. On the otherhand, for PAALA-3, PAALA-4, PAIBLA, andside groups.6 The presence of the long alkyl group

determines not only that the hexagonal packing is PAMELA the conformations experimentally ob-served can be explained in terms of the relativeabandoned but also that the 13/4 helix is the unique

conformation found in these systems. With the pur- CED calculated for schemes i 0 i / 3 and i 0 i/ 4. In particular, the intramolecular interactionspose of unraveling what are the constitutional hin-

dering of the 4/1 helix, a numerical approach to the between branched side groups of PAIBLA clearlyfavors the CED of the 4 /1 helix with respect toenergetic evaluation of the side-chain contributions,

which is described in Eqs. (3) and (4), has been the 13 /4 helix in this polymer. On the other hand,the 4 /1 helix appears to be not stable for PA-applied to 7-oligopeptides.MELA, in good agreement with experimental ob-servations. Finally, dipole moment computationsDH({CH2{)13/4 Å DHf (PAALA-4)13/4

(3) predict the 13 /4 helix to be the most stable con-0 DHf (PAALA-3)13/4

formation in solution for all the poly (b-L-aspar-tate ) s considered in this work.DH({CH2{)4/1 Å DHf (PAALA-4)4/1

(4)0 DHf (PAALA-3)4/1

We are indebted to the CEPBA for computational facili-ties. This work has been supported by DGICYT with

In these equations DHf (PAALA-4) andgrant PB93-0960.

DHf (PAALA-3) are the heats of formation forPAALA-4 and PAALA-3 respectively computed atthe AM1 level. Note that such approach gives theenergy gain afforded by the addition of a methylene REFERENCESunit in the side group for both the 13/4[DH({CH2{)13/4 ] and 4/1 [DH({CH2{)4/1 ]

1. Degrado, W. F. (1988) Adv. Protein Chem. 39, 51.helices. The resulting values were 06.7 kcal/2. Jain, R. & Chauan, V. C. (1996) Biopolymers (Pep-mol∗(CH2) and 06.8 kcal/mol∗(CH2) for the 13/

tide Sci.) 40, 105.4 and 4/1 helices respectively. Such a small energy 3. Fernandez-SantıB n, J. M., Munoz-Guerra, RodrıB -difference [É 0.1 kcal/mol∗(CH2)] is not enough guez-Galan, A., AymanıB , J., Lloveras, J., Subirana,to compensate the relative stability of the 13/4 he- J. A., Giralt, E. & Ptak, M. (1987) Macromoleculeslix, which is about 1 kcal/mol∗residue (see Figure 20, 62.4) . Furthermore, it should be recalled that the 4/1 4. Munoz-Guerra, S., Fernandez-SantıB n, J. M., Alegre,helix is unfavored from an entropic point of view C. & Subirana, J. A. (1989) Macromolecules 22,

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Alveraz, M., MartıB nez de Ilarduya, A. & Munoz-The results reported in the present work help ra-Guerra, S. (1995) Macromol. Chem. Phys. 196, 253.tionalize the conformational tendencies exhibited

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10. Lopez-Carrasquero, F., GarcıB a-Alvarez, M., Navas,the most stable structure for oligomers with aJ. J., Aleman, C. & Munoz-Guerra, S., submittedsmall number of residues and that their conforma-work.

tional preferences are largely determined by the 11. Navas, J. J., Aleman, C., Lopez-Carrasquero, F. &chemical nature of the side chain and the number Munoz-Guerra, S., submitted work.of residues comprised in the chain. For PAALA- 12. Fraser, R. D. B. & MacRae, T. P. (1973) in Confor-1 and PAALA-2 both energies and the CED dif- mation in Fibrous Proteins, Academic Press, Newferences between the 13 /4 and 17/4 helices are York.

13. Aleman, C. (1994) Biopolymers 34, 841.small, indicating that packing effects are respon-



14. Dewar, M. J. S., Zoebisch, E. G., Healy, E. F. & 19. Stewart, J. J. P. (1983) QCPE Bull. 3, 431.Stewart, J. J. P. (1985) J. Am. Chem. Soc. 107, 3902. 20. Weiner, S. J., Kollman, P. A., Nguyen, D. T. & Case,

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effect of the side group on the helix-forming tendency of α-alkyl-β-l-aspartamyl residues

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