Conformational investigation of α,β-dehydropeptides

Conformations of three series of model peptides: homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHCH₃ (Xaa=Phe, Val, Leu. Abu. Ala) as ivell as α,β-dehydro Ac-Pro-ΔXaa-NHCH_s [ΔXaa = (Z)-ΔPhe, ΔVal. (Z)-ΔLeu, (Z)-ΔAbu] were investigated by CD spectroscopy in 2 % dichloromethanecyclohexane, trifluoroethanol. water. and occasionally in other solvents. The spectra of homochiral peptides show a significant solvent dependence. Folded structures are present in 2% dichloromethane-cyclohexane and unordered ones occur in water. The folded conformers are of the inverse γ-turn type for all the peptides but Ac-Pro-L-Phe-NHCH₃ for which the type-I β-turn is preferred. The changes in the spectra of the heterochiral peptides are limited. The compounds adopt the typc-II β–turn in 2% dichloromethanecyclohexane, represented by class B spectra, and retain this conformation in water as well as in fluorinated alcohols but not always to a full extent. The CD spectra of the unsaturated peptides in 2%, dichloromethanecyclohexane, although they cannot be assigned to any common spectral class, must be attributed to the βII-turn conformation as determined for these coinpounds by NMR and IR spectroscopy. The CD spectra of dehydropeptides exhibit a considerable solvent dependence and suggest unordered structures in water.     

Conformations of peptides containing 1-aminocyclohexanecarboxylic acid (Acc6). Crystal structures of two model peptides

The crystal structures of two peptides containing 1-aminocyclohexanecarboxylic acid (Acc⁶) are described. Boc-Aib-Acc⁶-NHMe · H₂O adopts a β-turn conformation in the solid state, stabilized by an intramolecular 4 → 1 hydrogen bond between the Boc CO and methylamide NH groups. The backbone conformational angles (φ_Aib = – 50.3°, ψ_Aib = – 45.8°; φ_Acc6 = – 68.4°, ψ_Acc6 = – 15°) lie in between the values expected for ideal Type I or III β-turns. In Boc-Aib-Acc⁶-OMe, the Aib residue adopts a partially extended conformation (φ_Aib = – 62.2°, ψ_Aib = 143°) while the Acc⁶residue maintains a helical conformation (φ_Acc6 = 48°, ψ_Acc⁶= 42.6°). ¹H n.m.r. studies in CDCl₃ and (CD₃)₂SO suggest that Boc-Aib-Acc⁶-NHMe maintains the β-turn conformation in solution.     

Theoretical π-π* absorption and circular dichroic spectra of β-turn model peptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate π-π* absorption and circular dichroic spectra of β-turn model peptides in certain conformations. These include Ac-Gly-Gly-NHMe, Ac-L-Ala-L-Ala-NHMe, and Ac-L-Ala-Gly-NHMe in the standard β-turn conformations I, II, and III of Venkatachalam and cyclo(L-Ala-Gly-ε-aminocaproyl), cyclo(L-Ala-L-Ala—aminocaproyl), and cyclo(L-Ala-D-Ala-ε-aminocaproyl) in the minimum-energy conformations of Nemethy et al. Boltzmann average circular dichroic spectra of the cyclic compounds agree with experimental spectra in most respects. The results are compared with previous theoretical CD spectra for these molecules and with conformational assignments based on other evidence. Absorption spectra in the π-π* band are predicted to be moderately sensitive to conformation.     

Circular dichroic and immunological properties of human choriogonadotropin-β carboxyl terminal peptides

Circular dichroic spectra have been obtained in aqueous solution and in trifluoroethanol for several synthetic (non-glycosylated) human choriogonadotropin carboxyl terminal peptides of the β-subunit ranging in size from 10 residues to 40 residues. There was no evidence for formation of α-helicity or β-structure, but the spectra in 90% (v/v) trifluoroethanol were consistent with the occurrence of β-turns. The Chou-Fasman predictive rules also suggest a high probability of β-turns in these peptides which could result in the occurrence of repeating kinks. Disulfide-linked dimers were also investigated by circular dichroism, and there was evidence of stabilization of particular skewness of the disulfide dihedral angle depending upon the location of the disulfide bond. The single phenylalanyl residue at position 115 in the β-subunit also contributed to the circular dichroic spectra above 250 nm. Antibodies raised to a peptide consisting of residues 111–145 have been shown to contain two immunological determinants, but the sum of antibodies raised to separate determinant sequences do not equal those raised to the full length peptide. These data could reflect the existence of a conformation-related determinant on the 111–145 peptide or stearic hindrance of immunoglobulin binding of two antibodies to the same peptide.     

The evaluation of type I and type II β-turn mixtures

Circular dichroism (CD) and¹ H-{¹H}NOE spectra were obtained for Piv-Pro-Ser-NHCH₃(1),[Piv-(CH₃)₃-C-CO], Boc-Pro-Ser-NHCH₃ (2) and Boc-Val-Ser-NHCH₃ (3), to determine the solution conformation of these p-turn models. In the crystal, 1 and 3 adopt an ideal type I β-turn, while 2 is characterized by a semifolded backbone geometry incorporating a cis Boc-Pro tert-amide bond. The predominance of a β-turn conformation in solution was suggested for models 1-3 on the basis of ¹H-{¹H}NOE data. In a nonpolar solvent the prevailing trans rotamer form (>80%) of 2 has a β-turn conformation according to heteronuclear NOE measurement. Positive ¹H-{¹H} NOEs were detected between the H^α(Pro)/NH(Ser), Hα(Ser)/NH(Ser) and NH(NHCH₃3)/HN(Ser) protons in the trans Boc-Pro rotamer form of 2 at -20° in CDCl₃. Similar positive homonuclear NOE enhancements were also observed on the appropriate proton signals in other models, such as Boc-Val-Ser-NHCH₃ (3). Boc-Val-D-Ser-NHCH₃ (4) and Boc-Pro-D-Ser-NHCH₃ (5), in various solvents. The ¹H- {¹H)NOE experiments carried out in CD₃CN clearly showed that besides the type I (or III) β-turn structure, one of the main conformations of models 1-5 is close to the type II β-turn backbone geometry in a nonpolar solvent. Unexpectedly, the conformational mixture of models 1-3 were characterized by class C (helix-like) CD spectra, although class C spectra are generally only correlated with the type I β-turn conformation. These acyclic models are the first carefully investigated examples of -L-L- triamide systems, containing a significant amount of a type II β-turn, as well as the type I p-turn and, however, yielding a class C circular dichroism spectra. The CD spectra recorded for 3 and 4 in acetonitrile were ‘calibrated’ using the ¹H-{¹H}NOE data. Such a “calibration”, as well as the semi-quantitative CD and NMR comprehensive analyses, demonstrated that class C, class B, as well as class C’ CD spectra may be obtained from the linear combination of the same two-component spectra, with different conformational weights. Therefore, it is suggested that the extraction of the conformational components of such models, simply on the basis of their CD spectra, must be made with caution.     

Structural redesign and stabilization of the overlapping tandem β-turns of RNA polymerase II

Peptides representing single repeat units of the carboxy-terminal domain (CTD) of RNA polymerase II (Tyr-Ser-Pro-Thr-Ser-Pro-Ser-Tyr-NH₂, 1) contain overlapping Ser-Pro-Xaa-Xaa β-turn forming sites which permit their overall structure to closely resemble members of the quinoxaline class of antitumor DNA bisintercalators. We have modified this native sequence at the i+2 positions of each β-turn unit by substituting Gly or D-Ala in an attempt to preorganize this structure in aqueous solution. CD and NMR spectroscopic investigations confirmed the presence of type II β-turns within each of the substituted peptides in contrast to the native sequence which contains a relatively low population of turn structure. In addition, an examination of singly substituted peptides suggests that an increase in the population of β-turn structure within the amino-terminal Ser-Pro-Xaa-Xaa site also increased the formation of β-turn structure in the carboxy-terminal (unmodified) Ser-Pro-Xaa-Xaa site; in comparison, substitution in the carboxy-terminal site did not influence structure in the remaining portion of the peptide. Overall, these results suggest that the structures formed could provide unique. preorganized linkers for the construction of novel DNA-interactive bisintercalators. © Munksgaard 1996.     

Studies of repeating synthetic peptides designed to adopt a cross-β conformation

The conformational preferences of peptides forming parts of the sequence Val-Val-Asn-Pro-Gly-Gln-Val-Val have been studied by circular dichroism (CD) and nuclear magnetic resonance (n.m.r.) spectroscopy. The sequence is intended as a model for cross-β structures and keratins. CD spectra characteristic of type II β-bends are produced by Pro-Gly sequences: these have a maximum at 196–203 nm and a single minimum at 222–225 nm. Peptides with the sequence Asn-Pro-Gly have a CD spectrum attributable to a type I(III) β-bend with two minima at 200–205 nm and 220 nm respectively. N.m.r. data support the suggestion that the type I(III) bend is stabilised by H-bonding between the oxygen of the side-chain amide of Asn and the hydrogen of the main chain NH of the Gly (or other third) residue. Thus, sequences where such H-bonding is possible show shielding of the Asn amide protons, non-equivalence of C^βH₂ protons and low temperature dependencies of NH protons of the third residue for each peptide examined. Calculations of rotamer populations for the Asn amide side chain support these conclusions.     

Stereochemistry of peptides containing 1-aminocycloheptane-1-carboxylic acid (Ac7c)

The crystal structures of four peptides incorporating l-aminocycloheptane-l-carboxylic acid (Ac₇c) are described. Boc-Aib-Ac₇c-NHMe and Boc-Pro-Ac₇c-Ala-OMe adopt β-turn conformations stabilized by an intramolecular 4 × 1 hydrogen bond, the former folding into a type-I/III β-turn and the latter into a type-II β-turn. In the dipeptide esters, Boc-Aib-Ac₇c-OMe and Boc-Pro-Ac₇c-OMe, the Ac₇c and Aib residues adopt helical conformations, while the Pro residue remains semi-extended in both the molecules of Boc-Pro-Ac₇c-OMe found in the asymmetric unit. The cycloheptane ring of Ac₇c residues adopts a twist-chair conformation in all the peptides studied. ¹H-NMR studies in CDCl₃ and (CD₃)₂SO and IR studies in CDCl₃, suggest that Boc-Aib-Ac₇c-NHMe and Boc-Pro-Ac₇c-Ala-OMe maintain the β-turn conformations in solution.     

Conformation—activity correlations for chemotactic tripeptide analogs incorporating dialkyl residues with linear and cyclic alkyl sidechains at position 2

Five stereochemically constrained analogs of the chemotactic tripeptide incorporating l-aminocycloalkane-l-carboxylic acid (Ac_nc) and α, α-dialkylglycines (Deg, diethylglycine; Dpg, N, N-dipropylglycine and Dbg, N, N-dibutylglycine) at position 2 have been synthesized. NMR studies of peptides For-Met-Xxx-Phe-OMe (Xxx = Ac₇c. I: Ac₈c. II: Deg, III; Dpg, IV and Dbg, V; For, formyl) establish that peptides with cycloalkyl residues, I and II, adopt folded β-turn conformations in CDCl₃, and (CD³)₂SO. In contrast, analogs with linear alkyl sidechains, III-V, favour fully extended (C₅) conformations in solution. Peptides I-V exhibit high activity in inducing β-glucosaminidase release from rabbit neutrophils, with ED₅₀ values ranging from 1.4–8.0 × 10–¹¹. M. In human neutrophils the Dxg peptides III-V have ED₅₀ values ranging from 2.3 × 10^?8 to 5.9 × 10^?10 M, with the activity order being V>IV>III. While peptides I-IV are less active than the parent. For-Met-Leu-Phe-OH, in stimulating histamine release from human basophils, the Dbg peptide V is appreciably more potent, suggesting its potential utility as a probe for formyl peptide receptors. © Munksgaard 1996.     

Synthetic and conformational studies on dehydrophenylalanine containing model peptides

Four model dipeptides containing a Z-dehydrophenylalanine residue (Δ^ZPhe) at the C-terminal, Boc-X-Δ^Z Phe-NHMe (X = Ala (1), Gly (2), Pro (3), and Val (4)), have been synthesised and their solution conformations investigated by 270 MHz ¹H n.m.r. and i.r. spectroscopy. N.m.r. studies on these peptides clearly show the presence of intramolecularly hydrogen bonded structures in CHCl₃ solutions while such structures appear to be absent in the corresponding saturated peptides. This conclusion is also supported by i.r. studies. Studies of the nuclear Overhauser effect provided evidence for the occurrence of a significant population of β-turn structures in solvents like CDCl₃ and (CD₃)₂SO. The observed NOES are consistent with a major contribution from Type II β-turn structure in CDCl₃, while in (CD₃)₂SO solutions there is evidence of a partially extended structure also.     

Experimental studies and potential energy calculations of the blocked tetrapeptide Ac-Lys-Pro-Gly-Ile-NMA from the third loop of short-chain snake venom neurotoxins

The conformational space of the tetrapeptide Ac-Lys-Pro-Gly-Ile-NMA from the β-bend present in the third loop of short-chain snake venom neurotoxins was investigated with the aid of energy calculations, resulting in the identification of an ensemble of β-turn conformations. These results were compared with the experimentally determined conformations, as observed using NMR and CD spectroscopy. A random coil conformation of the peptide is indicated in polar hydrogen-bonding solvents. In less polar solvents the peptide backbone assumed a more rigid conformation, as reflected by the existence of at least a type II β-turn conformation.     

Motifs and conformational analysis of amino acid residues adjoining β-turns in proteins

Using a data set of 250 non-homologous high-resolution globular proteins, a systematic analysis of the conformations that precede and succeed (positions i and i+3) the various classical β-turn types has been carried out. The collective conformation of a specific β-turn type, including the flanking positions, termed motif, has been studied. In all the four turn types, the majority of examples are preceded and succeeded by extended conformation. Some of the other observations are: (1) In a type I β-turn, Gly at position i+ 3 has a higher favorability to occur with positive ø and does not prefer the major motif βα_R-α_R-β. (2) The left-handed alpha;-helical conformation (alpha;_L) is not preferred at both the flanking positions for type I'and II β-turns, (3) The β–β motif is favourable for all the turn types and the motif β–α_L very highly favourable for type I. © Munksgaard 1996.     

NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin

A NMR investigation in H₂0, TFE and DMSO of a conformationally constrained, potent decapeptide agonist of human C5a, YSFKDMPLaR (C5a₆₅-₇₄, Y65, F67, P71, d -Ala73) showed that its N-terminal region (YSFKD) exhibited an extended backbone conformation in H₂O and a more twisted conformation in both TFE/H₂O (30:70, v/v; referred to as TFE) and DMSO. The C-terminal region (MPLaR) of the peptide adopted compact, turn-like structures. In H₂O, the C-terminal region adopted a type II β-turn or a distorted type V/II β-turn involving residues PLaR. In the distorted type V/II β-turn, Leu72 exhibited a conformation typical of a type V β-turn, whereas D -Ala73 exhibited a conformation typical of a type II β-turn. The distorted type V/II β-turn overlapped with an inverse γ-turn involving residues MPL. In DMSO, the C-terminal region had the analogous inverse y-turn and the V/II γ-turn found in H₂O. In many of the DMSO structures, two inverse γ-turns in the MPL and PLa positions formed a double-inverse γ-turn. None of the turns observed in H₂O were present in TFE. However, in TFE, the PLa residues formed an inverse γ-turn. Overall, the turn-like structural motifs in the C-terminal region of the peptide in both H₂O and DMSO (but not in TFE) agreed with the biologically important conformations obtained earlier by the structure-function analysis of a panel of C5a agonist peptides. These motifs may represent key structural elements important for C5a agonist activity and may be used to design the next generation of C5a agonist and antagonist analogues. © Munksgaard 1998.     

Spectroscopic analysis of [Trp3]-β-casomorphin analogs Comparative structure conformation-activity studies

A series of [3-tryptophan]-β-casomorphin-5([Trp³]-β-CM-5) analogs were investigated by circular dichroism (CD) and fluorescence spectroscopy to explore their structure-conformation properties in solution. In addition, the comparative opioid activities of these compounds were evaluated using the in vitro guinea pig ileum (GPI) and mouse vas deferens (MVD) assays. Specifically, the pentapeptide sequence of [Trp³]-β-CM-5, H-Tyr-Pro-Trp-Pro-Gly-OH (I) was modified at Pro-2 and Pro-4 by d -Pro substitutions to provide two diastereometric analogs, [Trp³-d -Pro-4]-β-CM-5 (II) and [d -Pro^2,4,Trp³]-β-CM-5 (III). In the GPI and MVD assays, β-CM-5 effected IC₅₀ values of 1.3 μm and 8.9 μm , respectively, which confirmed its known μ/δ-selectivity on these two peripheral opioid receptor subtypes. The potencies of compounds I, II, and III were 0.2, 2.0, and < 0.005 relative to β-CM-5 on the GPI assay. Compounds I and II exhibited pronounced μ/δ-selectivities (> 18.9- and 12.4-fold respectively), whereas compound III was essentially inactive in both the GPI and MVD assays. CD studies of β-CM-5 and its [Trp³]-β-CM-5 analogs showed striking differences in their near-UV and far-UV spectra in aqueous or organic solvents. In the far UV CD spectra, weak (20%) α-helicity (maximum at 193 nm and minima at 208 and 222 nm) for β-CM-5 was obtained in trifluoroethanol (TFE); however, none of the [Trp³]-β-CM-5 analogs showed such CD bands. Of potential relevance to γ-turn or C₇ secondary structure was the observation of a strong negative band at 245 nm for compounds II and III which was not solvent-dependent in H₂O or TFE, whereas compound I showed this CD band exclusively in TFE. In the near-UV CD at 275 nm (Trp electronic transition), the relative order of intensities of this band were determined for the [Trp³]-β-CM-5 compounds to be II > I > III, which was identical to their relative biological potencies in both the GPI and MVD assays. Fluorescence energy transfer (FET) experiments of compounds I-III provided the intramolecular distances (r) between their Tyr (donor) to Trp (acceptor) side-chains, by the Förster method, and were as follows: [Trp³]-β-CM-5, r = 10.6Å; [Trp³, d -Pro⁴]-β-CM-5, r = 9.6Å; and [d -Pro^2,4,Trp³]-β-CM-5, r = 11.0Å. A rank order correlation existed between the Tyr-Trp intramolecular distances and biological activity with shorter distance corresponding to higher biological potency. Furthermore, based on the fluorescence lifetime data analysis (Globals software) of the [Trp³]-β-CM-5 analogs, which were best fitted to a double exponential decay model, the relative ranking of long (> 1.5 ns) lifetime fractions of these three compounds was II > I > III. In summary, detailed spectroscopic analysis of three [Trp³]-β-CM-5 diastereomeric analogs by CD and FET have provided intriguing data indicating a possible structure conformation-activity relationship among these μ/δ-selective opioid-mimetic compounds.     

Proline-containing β-turns

The conformations of the dipeptide t-Boc-Pro-d Ala-OH and the tripeptide tBoc-Pro-d Ala-Ala-OH have been determined in the crystalline state by X-ray diffraction and in solution by CD, n.m.r. and i.r. techniques. The unit cell of the dipeptide crystal contains two independent molecules connected by intermolecular hydrogen bonds. The urethane-proline peptide bond is in the cis orientation in both the molecular forms while the peptide bond between Pro and d Ala is in the trans orientation. The single dipeptide molecule exhibits a “bent” structure which approximates to a partial β-turn. The tripeptide adopts the 4 → 1 hydrogen-bonded type II β-turn with all trans peptide bonds. In solution, the CD and i.r. data on the dipeptide indicate an ordered conformation with an intramolecular hydrogen bond. N.m.r. data indicate a significant proportion of the conformer with a trans orientation at the urethane-proline peptide bond. The temperature coefficient of the amide proton of this conformer in DMSO-d₆ points to a 3 → 1 intramolecular hydrogen bond. Taken together, the data on the dipeptide in solution indicate the presence (in addition to the cis conformer) of a C₇ conformation which is absent in the crystalline state. The spectral data on the tripeptide indicate the presence of the type II β-turn in solution in addition to the nonhydrogen-bonded conformer with the cis peptide bond between the urethane and proline residues. The relevance of these data to studies on the substrate specificity of collagen prolylhydroxylase is pointed out.     

Force-field dependence of Boltzmann weighting factors on predicted π-π*circular dichroic spectra of cyclo(Gly-Pro-Gly)2

Semi-empirical energy calculations were performed for published conformations of cyclo(Gly-Pro-Gly)₂ using different force fields (DISCOVER cvff and cff91, AMBER, and CHARMM). The resulting potential energies were then used to create Boltzmann weighting factors for an ensemble of cyclo(Gly-Pro-Gly)₂ structures. The dipole interaction model was used to predict π-π* circular dichroic spectra (CD) for the individual structures of cyclo(Gly-Pro-Gly)₂. The Boltzmann weighting factors were applied to the individual spectra so that a composite spectrum was constructed to represent a CD arising from a collection of different structures in solution. Weighting factors determined from different force fields were compared. Boltzmann-weighted spectra better resembled the experimental CD than any calculated spectrum using only a single conformation of cyclo(Gly-Pro-Gly)₂. The structures most heavily weighted contained at least one type I β-turn.     

Stabilization of β-turn conformations in enkephalins

Stereochemical constraints have been introduced into the enkephalin backbone by substituting α-aminoisobutyryl (Aib) residues at positions 2 and 3, instead of Gly. ¹H n.m.r. studies of Tyr-Aib-Gly-Phe-Met-NH₂, Tyr-Aib-Aib-Phe-Met-NH₂ and Tyr-Gly-Aib-Phe-Met-NH₂ demonstrate the occurrence of folded, intramolecularly hydrogen bonded structures in organic solvents. Similar conformations are also favoured in the corresponding t-butyloxycarbonyl protected tetrapeptides, which lack the Tyr residue. A β-turn centred at positions 2 and 3 is proposed for the Aib²-Gly³analog. In the Gly²-Aib³analog, the β-turn has Aib³-Phe⁴as the corner residues. The Aib²-Aib³analog adopts a consecutive β-turn or 3₁₀ helical conformation. High in vivo biological activity is observed for the Aib²and Aib²-Aib³analogs, while the Aib³peptide is significantly less active.     

Conformationally restrained peptides: crystal structure of tert-butyloxycarbonyl-L-alanyl-D-alanyl-D-aminosuccinyl-glycyl-L-alanine methyl ester

The solid-state structure of a heterochiral peptide embodying a D-aminosuccinyl peptide (D-ASU) and a D-Ala was studied in order to analyse the effects of Asu and amino acids with inverse chirality on peptide conformation. The crystal structure has been determined by X-ray diffraction techniques and refined to a final R factor of 0.043. The molecule adopts an unusual overall 'S-shape’ conformation due to two consecutive type II β-turns. In this molecule it is possible to compare a type II β-bend conformation (L-Ala¹-D-Ala²) favoured by the presence of a D-residue at second corner to a type II β-turn (D-Asu³-Gly⁴) favoured by the presence of a D-ASU residue at first corner. In agreement with previous studies, this structure confirms that the Asu has a high propensity to adopt a type II or II′β-bend conformation and that it may be used as a strong determinant of these structural motifs. © Munksgaard 1996.     

Conformational investigation of αβ-dehydropeptides

Solution conformations of three series of model peptides, homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHcH₃ (Xaa = Val, Phe, Leu, Abu. Ah) as well as αβ-unsaturated Ac-Pro-ΔXaa-NHCH₃ [Δ Xaa =ΔVal, (Z)-ΔPhe, (Z)-ΔLeu, (Z)-ΔAbu] were investigated in CDCl₃ and CH₂Cl₂ by ¹H-, ¹³C-NMR, and FTIR spectroscopy. NH stretching absorption spectra, solvent shifts Δδ for NH (Xaa) and NHCH₃ on going from CDCl₃ to (CD₃)₂SO, diagnostic interresidue proton NOEs, and trans-cis isomer ratios were examined. These studies performed showed the essential difference in conformational propensities between homochiral peptides (L-Xaa) on the one hand and heterochiral (D-Xaa) and αβ-dehydropeptides (ΔXaa) on the other. Former compounds are conformationally flexible with an inverse γ-bend, a β-turn, and open forms in an equilibrium depending on the nature of the Xaa side chain. Conformational preferences of heterochiral and αβ-dehydropeptides are very similar, with the type-II β-turn as the dominating structure. There is no apparent correlation between conformational properties and the nature of the Xaa side chain within the two groups. The β-turn formation propensity seems to be somewhat greater in αβ-unsaturated than in heterochiral peptides, but an estimation of β-folded conformers is risky.     

Studies on β-turn of peptides

The effect of changing 1st and 4th amino acid residues on β-turn preference of tetrapeptide sequences was studied by use of CD spectra of the chromophoric derivatives, which have Dnp- and pNA-groups as the amino and carboxyl substituents, respectively. The effect was examined with the tetrapeptides having such sequences at the 2nd and 3rd positions as -L-Pro-L-Asn-, -L-Pro-Gly-, -L-Pro-D-Ala-, -L-Ala-D-Leu-, -L-Ala-L-Pro-, and -D-Ala-L-Pro-. The β-turn preferences estimated from the CD intensities of the bands due to exciton interaction were found to depend largely on the configurations of the 1st and 4th amino acid residues. When 1st and 2nd (or 3rd and 4th) residues had the same configuration, decreased intensity of the CD band was observed even if the internal sequence had high β-turn preference. Terminal Gly residues were favorable for the β-turn conformation in many of the tetrapeptide sequences examined.