Cation binding cyclic peptides composed of imino acid residues

Cyclo(L -Pro-Sar)_n (n = 2–4) with moderate flexibility and hydrophobicity of molecular structure was synthesized, and the characteristics of these cyclic peptides and their metal complexes in acetonitrile were investigated in connection with the residual properties using ¹³C-nmr measurements. The cyclic tetrapeptide cyclo(L -Pro-Sar)₂ showed a sterically hindered phenomenon in acetonitrile in which the amide backbone adopted a cis-trans-cis-trans sequence. The cyclic hexapeptide cyclo(L -Pro-Sar)₃ existed as a mixture of several conformers whose interconversion is slow on the nmr time scale, including cis-cis-trans and/or cis-trans-trans arrangement of the Sar-Pro bond. Finally, it was demonstrated that the cyclic octapeptide cyclo(L -Pro-Sar)₄ behaved as a mixture of multiple conformers which allowed for cis-trans isomerism about the Pro-Sar peptide bond, of which 20–30% had the all-cis Sar-Pro bond isomer and the remaining 70–80% had one (or more) cis Sar-Pro bond isomer. ¹³C-nmr spectra also demonstrated that cyclo(L -Pro-Sar)_n (n = 3,4) formed a 1:1 ion complex whose conformation was characterized by an all-trans peptide bond in the presence of excess metal salt. Cation binding studies, using CD measurements, established that the ion selectivity of cyclo(L -Pro-Sar)₄ in acetonitrile decreased in the order, Ba²⁺ > Ca²⁺ > Na⁺ > Mg²⁺ > Li⁺.     

Cyclo(D-Pro-L-Pro-D-Pro-L-Pro): Structural properties and cis/trans isomerization of the cyclotetrapeptide backbone

Combinations of L - and D -proline residues are useful compounds for finding new structures and properties of cyclic peptides. This is demonstrated with one striking example, the cyclic tetrapeptide c(D -Pro-L -Pro-D -Pro-L -Pro). For this molecule composed of strictly alternating D - and L -configurated residues, a highly symmetrical structure is expected, which should be an optically inactive meso-form. Cyclization of the enantiomeric pure linear precursor D -Pro-L -Pro-D -Pro-L -Pro, however, yields a racemic mixture of two enantiomeric cyclotetrapeptides, both with twofold symmetry and a cis–trans–cis–trans sequence of the peptide bonds. Remarkably, this formation of a racemate was not caused by racemization, but by cis/trans isomerization of all peptide bonds in the ring. This process may occur in the linear precursor during the ring formation (cyclization of conformers with trans–cis–trans or cis–trans–cis arrangement of the amide bonds) as well as in the enantiomeric pure cyclic tetrapeptide at higher temperature. In the latter case, an all-cis structure should exist as the intermediate, which can form a cis–trans–cis–trans sequence in two equivalent ways, leading finally to two enantiomeric cyclotetrapeptides. In the first one, the cis peptide bonds are attributed to the L -residues and the trans peptide bonds to the D -residues; in the second one, the cis bonds belong to the D and the trans bonds to the L -residues. The mixture of these two enantiomers does not crystallize in the racemic form, but in enantiomeric pure separate crystals. The structural properties could be proved by ¹H- and ¹³C-nmr spectroscopy and x-ray analysis. The cis/trans isomerization process was confirmed by optical rotation measurements and CD spectroscopy, as well as DREIDING model studies. Calorimetric measurements in the solid state suggest the existence of the expected all-cis intermediate. The backbone conformation of the 12-membered medium-sized ring shows only slight deviations—up to 6° —from the planarity of the peptide bonds. On the other hand, the four pyrrolidine rings show different types of puckering of the C_γ or the C_β atoms.     

15N-nmr spectroscopy. 20. Cis/trans isomerism and neighboring residue effects of proline-containing peptides

Five N-protected tetrapeptide esters of the structure Gly-Pro-X-X*-O-methyl were synthesized in such a way that one of the two variable amino acid residues (X) was isotopically enriched in ¹⁵N (denoted by*). The variable amino acids are glycine, alanine, leucine, valine, and phenylalanine. For the natural abundance ¹⁵N-nmr spectra of these tetrapeptide derivatives in methylene chloride only the signals of the Gly-Pro trans isomer were found. In a 2:1 mixture of acetone and dimethylsulfoxide, signals for both the cis and trans isomers were observed. Three of the five tetrapeptide derivatives show cis/trans splitting of all four nitrogen signals. The ¹⁵N-nmr spectra of Z-Pro-Pro-OH and of (D ,L -proline)_n were measured in a 2:1 mixture of acetone and dimethylsulfoxide as well as in water. The effects of solvents and neighboring residues and the influence of the cis/trans isomerism on the nmr spectra are discussed. The determination of the cis/trans equilibria and the assignment of the ¹⁵N-nmr signals of all oligopeptides were achieved by selective isotopic enrichment and by means of ¹³C-nmr spectra.     

Cyclic peptides. XVIII. 13C spin-lattice relaxation times of (X-pro-Y)2 cyclic hexapeptides

¹³C spin-lattice relaxation times (T₁'s) of four cyclic hexapeptides of sequence, (X-L -Pro-Y)₂, are reported. The T₁'s of the protonated carbons, which undergo dipolar relaxation, are interpreted qualitatively in terms of the overall tumbling motion of the molecule and in terms of internal motion. It is found that three of the cyclic hexapeptides, those which adopt all-trans β-conformers, tumble isotropically and appear to lack internal motion in the peptide backbone. The method of Torchia and Lyerla was applied to these compounds in order to compare the mobility of the proline rings. The results show that the sequence and particular type of β-turn present affect the internal motion of the Pro ring. Data on a fourth cyclic hexapeptide, which occurs in a conformation with two-cis X-Pro bonds, suggests that internal motion of the backbone contributes an additional frequency component to the motion of the Y residue α-carbons. A consideration of the mobility of the proline rings in the conformer with two-cis peptide bonds revealed that they are significantly more rigid in the two-cis structure than in the all-trans.     

Secondary structure of peptides: 15. 13C n.m.r. CP/MAS study of solid elastin and proline-containing copolyesters

In order to study the chemical shifts and the cis—trans isomerism of prolyl units neighbouring glycine or other amino acids, 75.4 MH_z¹³C nuclear magnetic resonance (n.m.r.) cross-polarization/magic angel spinning (CP/MAS) spectra of the following solid oligopeptides and sequence polypeptides were measured: Z-Gly-Pro-OH,Z-Gly-Pro-Gly-Gly-OEt,Z-Gly-Pro-Ala-Ala-OMe,(Gly-Pro-Gly)_n,(Gly-Pro-Ala)_n,(β-Ala-Pro)_n and $\text{(δ-Ava-Pro)}{}_{\mathrm{<mtext>n</mtext>}}\text{(δ-Ava=δ-}\text{aminovaleric acid}$). Whereas all these oligo- and polypeptided contain exclusively trans X-Pro bonds, both cis and trans peptide bonds were found in a polypeptide prepared by copolymerization of glycine- and $\text{proline-}\text{N}\text{-carboxyanhydrides}$ in pyridine. On the basis of these model compounds, the ¹³C n.m.r. CP/MAS spectra of solid elastin allows the following conclusions. Almost all X-Pro bonds assume the trans conformation, most alanine and leucine units form α-helical chain segments, whereas only a small fraction of β-sheet structure is present. A 30.3 MHz ¹⁵N n.m.r. CP/MAS spectrum of solid elastin confirms that ～25% of all amino acids assume the α-helical structure. A model of elastin is discussed consisting of an amorphous phase, α-helical chain segments and helical segments of still unknown pitch.     

1H- and 13C-nmr investigations on cis–trans isomerization of proline peptide bonds and conformation of aromatic side chains in H-Trp-(Pro)n-Tyr-OH peptides

¹H and ¹³C high-resolution nmr spectra of cationic, zwitterionic, and anionic forms of the peptides: H-Trp-(Pro)_n-Tyr-OH, n = 0-5, and H-Trp-Pro-OCH₃ were obtained in D₂O solution. Analysis of H^α(Pro₁), H^α(Trp), C^γ(Pro), H^ε(Tyr), and H^δ(Trp) resonances provided evidence for the presence of two predominant backbone isomers: the all-trans one and another with the Trp-Pro peptide bond in cis conformation; the latter constituted about 0.8 molar fraction of the total peptide (n > 1) concentration. Relative content of these isomers varied in a characteristic way with the number of Pro residues and the ionization state of the peptides. The highest content of the cis (Trp-Pro) isomer, 0.74, was found in the anionic form of H-Trp-Pro-Tyr-OH; it decreased in the order of: anion ? zwitterion ≈ cation, and with the number of Pro residues to reach the value of 0.42 in the cationic form of H-Trp- (Pro)₅-Tyr-OH. Isomerization equilibria about Pro-Pro bond(s) were found to be shifted far (?0.9) in favor of the trans conformation. Interpretation of the measured vicinal coupling constants J_α?β′ and J_α?β″ for C^αH-C^βH₂ proton systems of Trp and Tyr side chains in terms of relative populations of g⁺, g^?, and t staggered rotamers around the χ₁ dihedral angle indicated that in all the peptides studied (a) rotation of Trp indole ring in cis (Trp-Pro) isomers is strongly restricted, and (b) rotation of Tyr phenol ring is relatively free. The most preferred χ₁ rotamer of Trp (0.8-0.9 molar fraction) was assigned as the t one on the basis of a large value of the vicinal coupling constant between the high-field H^β and carbonyl carbon atoms of Trp, estimated for the cis (Pro₁) form of H-Trp-Pro-Tyr-OH from a ¹H, ¹³C correlated spectroscopy ¹H detected multiple quantum experiment. This indicates that cis ? trans equilibrium in the Trp-Pro fragment is governed by nonbonding interactions between the pyrrolidine (Pro) and indole (Trp) rings. A molecular model of the terminal cis Trp-Pro dipeptide fragment is proposed, based on the presented nmr data and the results of our molecular mechanics modeling of low-energy conformers of the peptides, reported elsewhere. © 1993 John Wiley & Sons, Inc.     

Hybridization Studies with Chiral Peptide Nucleic Acids

A novel class of chiral peptide nucleic acids has been synthesized in which the sugar-phosphate backbone of DNA has been replaced with the glycyl-proline backbone of both the - and the -configurations, nucleobases being attached through the 4-position of proline withcis- andtrans-stereochemistry. TheT₁₀homopolymers withcis-stereochemistry in the - and -series bind strongly to poly(dA) withT_mvalues of 69 and 70°C, respectively. They bind more strongly to poly(rA) withT_mvalues of 73 and 72°C, respectively, and with apparent 1:1 stoichiometry. Using a mixed sequence decamer it was found that the thermal stability of the chiral peptide nucleic acid/oligonucleotide complex was comparable to that formed by Nielsen's polyamide nucleic acid.     

Nmr studies of the molecular conformations in the linear oligopeptides H-(L-Ala)n-L-Pro-OH

The molecular conformations of the linear oligopeptides H-(L -Ala)_n-L -Pro-OH, with n = 1,2 and 3, have been investigated. ¹³C nmr observation of the equilibrium between the cis and trans forms of the Ala-Pro peptide bond indicated the occurrence of nonrandom conformations in solutions of these flexible peptides. The formation of the nonrandom species containing the cis form of the Ala-Pro bond was found to depend on the deprotonation of the carboxylic acid group of proline, the solvent, and the ionic strength in aqueous solution. The influence of intramolecular hydrogen bonding on the relative conformational energies of the species containing the cis and trans Ala-Pro peptide bond was studied by comparison of the peptides H-(Ala)_n-Pro-OH with analogous molecules where hydrogen bond formation was excluded by the covalent structure. In earlier work a hydrogen bond between the protonated terminal carboxylic acid group and the carbonyl oxygen of the penultimate amino acid residue had been suggested to stabilize conformations including trans proline. For the systems described here this hypothesis can be ruled out, since the cis:trans ratio is identical for molecules with methyl ester protected and free protonated terminal carboxylic acid groups of proline. Direct evidence for hydrogen bond formation between the deprotonated terminal carboxylic acid group and the amide proton of the penultimate amino acid residue in the molecular species containing cis proline was obtained from ¹H nmr studies. However, the cis:trans ratio of the Ala-Pro bond was not affected by N-methylation of the penultimate amino acid residue, which prevents formation of this hydrogen bond. Overall the experimental observations lead to the conclusion that the relative energies of the peptide conformations including cis or trans proline are mainly determined by intramolecular electrostatic interactions, whereas in the molecules considered, intramolecular hydrogen bonding is a consequence of specific peptide backbone conformations rather than a cause for the occurrence of energetically favored species. Independent support for this conclusion was obtained from model consideration which indicated that electrostatic interactions between the terminal carboxylic acid group and the carbonyl oxygen of the penultimate amino acid residue could indeed account for the observed relative conformational energies of the species containing cis and trans proline, respectively.     

The beta-strand-loop-beta-strand conformation is marginally populated in beta2-microglobulin (20-41) peptide in solution as revealed by replica exchange molecular dynamics simulations

Solid-state NMR study shows that the 22-residue K3 peptide (Ser²⁰-Lys⁴¹) from β₂-microglobulin (β₂m) adopts a β-strand-loop-β-strand conformation in its fibril state. Residue Pro³² has a trans conformation in the fibril state of the peptide, while it adopts a cis conformation in the native state of full-length β₂m. To get insights into the structural properties of the K3 peptide, and determine whether the strand-loop-strand conformation is encoded at the monomeric level, we run all-atom explicit solvent replica exchange molecular dynamics on both the cis and trans variants. Our simulations show that the conformational space of the trans- and cis-K3 peptides is very different, with 1% of the sampled conformations in common at room temperature. In addition, both variants display only 0.3-0.5% of the conformations with β-strand-loop-β-strand character. This finding, compared to results on the Alzheimer's Aβ peptide, suggests that the biases toward aggregation leading to the β-strand-loop-β-strand conformation in fibrils are peptide-dependent.     

Synthesis and conformation of the cyclic octapeptides cyclo(Phe-Pro)4, cyclo(Leu-Pro)4, and cyclo[Lys(Z)-Pro]4

Cyclic octapeptides, cyclo(X-Pro)₄, where X represents Phe, Leu, or Lys(Z), were synthesized and their conformations investigated. A C₂-symmetric conformer containing two cis peptide bonds was found in all of these cyclic octapeptides. The numbers of available conformations due to the cis–trans isomerization of Pro peptide bonds depended on the nature of the solvent and X residue: they decreased in the following order: cyclo[Lys(Z)-Pro]₄ > cyclo(Leu-Pro)₄ > cyclo(Phe-Pro)₄ in CDCl₃. ¹³C spin-lattice relaxation times (T₁) of these cyclic octapeptides were measured, and the contribution of segmental mobility to T₁ was found to vary with the nature of the X residue.     

13C- and 1H-nmr evidence for all-cis peptide bonds in cyclic tetrapeptide cyclo(L-Pro-Sar)2

Conformations of the cyclic tetrapeptide cyclo(L -Pro-Sar)₂ in solution were studied by ¹H- and ¹³C-nmr spectrometry and model building. The nmr data provide definite evidence that this cyclic peptide exists chiefly in two conformations, namely, a C₂-symmetric conformation and an asymmetric structure. The former was demonstrated to be predominant in polar solvents (100% in Me₂SO-d₆). This structure contains all cis-peptide bond linkages and all trans′ Pro C^α?CO bonds. It represents the first cyclic tetrapeptide in which all four peptide bonds have been found in the cis-conformation. As the polarity of the solvent decreases, the population of C₂-symmetric conformers decreases (88% in CD₃CN and 65% in CDCl₃). At the same time, a minor asymmetric conformer, characterized by cis-cis-cis-trans peptide bond sequences (two cis Sar-Pro bonds, one cis Pro-Sar bond, and one trans Pro-Sar bond), is seen to increase (9% in CD₃CN and 30% in CDCl₃). A proposed predominant conformation in solution for cyclo(L -Pro-Sar)₂ was compared with a crystal structure, as reported in an accompanying paper. Both structures show striking overall similarities.     

Triple helix–coil transition of covalently bridged collagenlike peptides

The thermal triple helix–coil transition of covalently bridged collagenlike peptides with repeating sequences of (Ala-Gly-Pro)_n, n = 5–15, was studied optically. The peptides were soluble in water/acetic acid (99:1) and were found to form triple-helical structures in this solvent system beginning with n = 8. The thermodynamic analysis of the transition equilibrium curves for n = 9–13 yielded the parameters ΔH°_s = ?7.0 kJ per tripeptide unit, ΔS°_s = ?23.1 J deg^?1 mol^?1 per tripeptide unit for the coil-to-helix transition, and the apparent nucleation parameter σ ? 5 × 10^?2. It was suggested through double-jump temperature experiments that the rate-limiting step during refolding is not only influenced by the difficulties of nucleation, but also by cis–trans isomerization of the Gly-Pro peptide bond.     

Conformational properties of the sequential polyproline analogs poly(Pro-Aze-Pro) and poly(Aze-Pro-Aze)

The lack of the positive band at around 226 nm in the CD spectra of poly(prolyl-azetidine-2-carbonyl-proline) in trifluoroethanol and of poly(azetidine-2-carbonyl-prolyl-azetidine-2-carboxylic) acid in F₃EtOH and water, the hyperchromism of the absorption maximum at about 202 nm, and the extremely small intensity of the C^β-Pro, C^γ-Pro, and C^β-Aze signals for the cis peptide bonds in the ¹³C nmr spectrum of poly(Pro-Aze-Pro) in F₃EtOH indicate that both polyproline analogs exist as disordered chains in this solvent, the trans peptide group being maintained. The disordering of the chains is attributed to an increase in the accessible range of ψ due to the reduced dimensions of the square ring of L -azetidine-2-carboxylic acid residue relative to the pyrrolidine ring of proline and to strong interactions of the haloalcohol with the peptide groups of the chains.     

Intramolecular proton transfer in adenine imino tautomers

The electronic structural impact on intramolecular proton transfer in the cis- and trans-imino N7 and N9 tautomers of adenine (A) has been studied quantum mechanically, using density functional theory (B3LYP/TZVP, SAOP/TZ2P, LB94/TZ2P) and Green function (OVGF/TZVP) models. It is found that proton transfer does not significantly change isotropic properties but has profound impact on electron distributions of the species through anisotropic properties. The relative energies with respect to the canonical A tautomer (amino-9H), ΔE, for imino 7Hcis, imino 7Htrans, imino 9Hcis and imino 9Htrans are calculated as 16.15, 16.43, 18.46 and 13.80 kcal mol^? 1 (B3LYP/TZVP model) and some minor changes in perimeters of the purine ring is also observed. The Hirshfeld atomic charges indicate that whether a proton attached to N₍₇₎ or N₍₉₎ causes a significant local charge redistribution. However, these charges are insensitive to cis–trans proton transfer. Condensed Fukui function reveals N₍₁₀₎ and C₍₈₎ as the most electrophilic reactive site among N- and C-atom sites, respectively. We also found that proton transfer significantly alters in-plane σ orbitals, rather than out of plane π orbitals including the frontier orbital 6a″. Moreover, orbital based responses to various proton transfers are presented: the orbital 29a′ (HOMO-1) is a signature orbital differentiating all the four tautomers. Orbital 27a′ is a site (N₍₇₎ and N₍₉₎) sensitive orbital, whereas orbital 22a′ is only sensitive to proton orientation on the imino group = N–H.     

Minor Constituents of Japanese Ho-Leaf Oil

The main component of Japanese Ho-leaf oil has been shown to be (?)-linalool (80~90%), and the following twenty minor constituents newly have been identified; methyl vinyl ketone, methyl isobutyl ketone, mesityl oxide, β-pinene, myrcene, (+)-limonene, cis- and trans-ocimene, n-hexanol, cis-3-hexenol, cis- and trans-linalool oxide, (?)-1-terpinen-4-ol, (+)-cis and (+)-trans-2,6,6-trimethyl-2-vinyl-5-hydroxytetrahydropyran, citronellol, nerol, (+)-β-selinene, (+)-tagetonol and (?)-trans-hotrienol. (+)-Tagetonol and (?)-trans-hotrienol have been demonstrated to be (+)-3,7-dimethyl-3-hydroxy-1-octen-5-one (III) and (3R)-(?)-trans-3,7-dimethyl-3-hydroxy-1,5,7-octatriene (IX), respectively.     

Multiple interconverting conformers of the cyclic tetrapeptide tentoxin, [cyclo-(L-MeAla1-L-Leu2-MePhe[(Z)Δ]3-Gly4)], as seen by two-dimensional 1H-nmr spectroscopy

The conformations of the phytotoxic cyclic tetrapeptide tentoxin [cyclo-(L -MeAla¹-L -Leu²-MePhe[(Z)Δ]³-Gly⁴ )] have been studied in aqueous solution by two-dimensional proton nmr at various temperatures. Contrary to what is observed in chloroform, tentoxin exhibits multiple exchanging conformations in water. Aggregation phenomena were also observed. Four conformations with different proportions (51, 37, 8, and 4%) were observed at ?5°C. Models were constructed from nmr parameters and restrained molecular dynamics simulations. All the models exhibit cis-trans-cis-trans conformation of the amide bond sequence. The conversion from one form to another is accomplished by a conformational peptide flip consisting of a 180° rotation of a nonmethylated peptide bond. © 1995 John Wiley & Sons, Inc.     

Molecular Basis for Auto- and Hetero-catalytic Maturation of a Thermostable Subtilase from Thermophilic Bacillus sp. WF146

The proform of the WF146 protease, an extracellular subtilase produced by thermophilic Bacillus sp. WF146, matures efficiently at high temperatures. Here we report that the proform, which contains an N-terminal propeptide composed of a core domain (N*) and a linker peptide, is intrinsically able to mature via multiple pathways. One autocatalytic pathway is initiated by cis-processing of N* to generate an autoprocessed complex N*-I^WT, and this step is followed by truncation of the linker peptide and degradation of N*. Another autocatalytic pathway is initiated by trans-processing of the linker peptide followed by degradation of N*. Unlike most reported subtilases, the maturation of the WF146 protease occurs not only autocatalytically but also hetero-catalytically whereby heterogeneous proteases accelerate the maturation of the WF146 protease via trans-processing of the proform and N*-I^WT. Although N* acts as an intramolecular chaperone and an inhibitor of the mature enzyme, the linker peptide is susceptible to proteolysis, allowing the trans-processing reaction to occur auto- and hetero-catalytically. These studies also demonstrate that the WF146 protease undergoes subtle structural adjustments during the maturation process and that the binding of Ca²⁺ is required for routing the proform to mature properly at high temperatures. Interestingly, under Ca²⁺-free conditions, the proform is cis-processed into a unique propeptide-intermediate complex (N*-I^E) capable of re-synthesis of the proform. Based on the basic catalytic principle of serine proteases and these experimental results, a mechanism for the cis-processing/re-synthesis equilibrium of the proform and the role of the linker peptide in regulation of this equilibrium has been proposed.     

A Stereoselective Synthesis of Antimycinone A3 and Its Stereoisomers

Antimycinone A₃, which is a neutral fragment of mild alkaline hydrolysate of antimycin A₃, and its stereoisomers were synthesized stereoselectively from methyl trans-2-n-butylpent-3-enoate or methyl cis-2-n-butylpent-3-enoate, and natural antimycinone A₃ was proved to possess Hα-Hβ and Hβ-Hγ trans configuration.     

Stereochemical studies on cyclic peptides. IX. Conformational studies on cyclic tetrapeptides containing alternating cis and trans peptide units

Conformational analyses of cyclic tetrapeptides consisting of alternating cis and trans peptide units have been made using contact criteria and energy calculations. This study has been restricted to those structures having a symmetry element in the backbone ring, such as a twofold axis (d) or a center of inversion (i). There are five main results. (1) There are two distinct types of conformations, which are stereochemically favorable corresponding to each of twofold and inversion-symmetrical structures, designated as d₁, d₂ (for twofold symmetrical) and i₁, i₂ (for inversion-symmetrical). Among these, the i₁ type has the lowest energy when glycyl residues occur at all four α-carbon atoms. (2) With the glycyl residue at all four α-carbon atoms, methyl substitution at the cis peptide nitrogen atoms is possible in all the four types, whereas the substitution at trans peptide nitrogen atoms is possible only for the i₁ type. Thus only in the i₁ type can all the nitrogen atoms be methylated simultaneously. The conformation of the molecule in the crystal structure of cyclotetrasarcosyl belongs to the i₁ type. (3) When alanyl residues occur at all four α-carbon atoms, the possible symmetrical type is dependent on the enantiomorphic form and the actual sequence of the alanyl residues. (4) The methyl substitution at peptide nitrogen atoms for cyclic tetrapeptides having alanyl residues causes more stereochemical restriction in the allowed conformations than with glycyl residues. (5) The prolyl residue can be incorporated favorably at the cis-trans junction of both d and i types of structures. The results of the present study are compared with the data on cyclic tetrapeptides available from the crystal structure and nmr studies. The results show an overall agreement both regarding the type of symmetry and the conformational parameters.     

Steric effects of cis-trans isomerism on neighboring residues in proline oligopeptides: A 13C-nmr study of conformational heterogeneity in linear tripeptides

A series of proline-containing linear oligopeptides (4 dipeptides and 15 tripeptides) were synthesized and examined in aqueous and nonaqueous solutions using ¹³C-nmr spectroscopy. Spectra of linear tripeptides showing cis-trans isomerism about the X-Pro bond (X = Pro, Gly, and Ala) also show neighboring effects on the chemical shifts of residues both preceding and following the prolyl moiety. The extent of cis-trans isomerism observed about the X-Pro peptide bond correlates not only with the nature of X, but also depends on the size of the residue following proline; the larger substituents favor an increase in cis content about the X-Pro bond.