Stereochemical studies of cyclic peptides. XIV. Conformational analysis of cyclic tripeptides

Abstract

Conformational variety in cyclic tripeptides was examined using a combination of stereochemical and energy minimization methods. Four different conformations were found possible: (i) a threefold symmetrical one with all peptide units in cis configuration, with very little nonplanarity; (ii) an asymmetrical one with all cis units and with a larger nonplanarity (ccc); and (iii) two possible conformations with two cis and one trans peptide unit, (cct)₁ and (cct)₂. All these conformations can accommodate both sarcosyl and prolyl residues, which are known to occur in cis peptide units. The symmetric and the (cct)₂ conformations can accommodate only a homo-isomeric sequence of prolyl residues, and the other two asymmetric conformations (ccc) and (cct)₁ can accommodate hetero-isomeric sequence of Pro. In order to relieve some severe steric hindrances cis peptide units show a need-based flexibility in the peptide bond angles. All the four conformations are known to occur in solid state as well and the results obtained compare reasonably well with the available crystal structure information.