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Nmr studies of the molecular conformations in the linear oligopeptides H‐( L ‐Ala) n ‐ L ‐Pro‐OH
Author(s) -
Grathwohl Christoph,
Wüthrich Kurt
Publication year - 1976
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.1976.360151013
Subject(s) - chemistry , protonation , hydrogen bond , deprotonation , intramolecular force , stereochemistry , peptide bond , carboxylic acid , molecule , residue (chemistry) , proline , amide , covalent bond , peptide , aqueous solution , amino acid , organic chemistry , ion , biochemistry
The molecular conformations of the linear oligopeptides H‐( L ‐Ala) n ‐ L ‐Pro‐OH, with n = 1,2 and 3, have been investigated. 13 C 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 1 H 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.