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

✍ Scribed by G. Manjula; C. Ramakrishnan

• Publisher: Wiley (John Wiley & Sons)
• Year: 1979
• Tongue: English
• Weight: 760 KB
• Volume: 18
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.1979.360180309

✦ Synopsis

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 d l , d z (for twofold symmetrical) and il, iz (for inversion-symmetrical). Among these, the i l type has the lowest energy when glycyl residues occur a t all four a-carbon atoms. ( 2) With the glycyl residue a t all four a-carbon atoms, methyl substitution a t the cis peptide nitrogen atoms is possible in all the four types, whereas the substitution a t trans peptide nitrogen atoms is possible only for the i l type. Thus only in the i l type can all the nitrogen atoms be methylated simultaneously. The conformation of the molecule in the crystal structure of cyclotetrasarcosyl belongs to the il type. (3) When alanyl residues occur a t all four a-carbon atoms, the possible symmetrical type is dependent on the enantiomorphic form and the actual sequence of the alanyl residues. (4) The methyl substitution a t 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 a t 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.