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

Abstract

SynopsisConformational 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.

Conformational studies on β‐bend containing a cis peptide unit

“…5 along with the contact map for a system of linked trans-cis peptide units with L-Ala at the junction (21). 5 along with the contact map for a system of linked trans-cis peptide units with L-Ala at the junction (21).…”

“…5 along with the contact map for a system of linked trans-cis peptide units with L-Ala at the junction (21). (21)). The plot shows that all the non Gly residues occur at the top left quadrant of the map, well within the allowed region.…”

“…The example occurring in cyclic pentapeptide (Ala-Pro-Gly-D-Phe-Pro) (example 9 of Table 6 ) falls just outside the allowed region, in X-cis-Pro at X MEC 13. 14. The two open squares in the right half of the map correspond to Gly residues and this region is allowed for glycyl residue at the trans-cis junction (21). 16.…”

Conformation and formation tendency of the cyclotetrapeptide cyclo(D‐pro‐D‐pro‐L‐pro‐L‐pro): Experimental results and molecular modeling studies

“…The 'H-nmr showed in the C,-H region two downfield shifted signals that represent the structure evidenced by x-ray analysis: 6 = 4.49, 4.52 ( c i s ) and 5.09, 5.11 ppm ( t r a n s ) . Furthermore, there should be a minor conformer (ratio 1 : 6 ) , which is indicated by a somewhat broadened doublet located at 6 = 4.63, 4.60 (C,-H, cis, 3 H ) , and a four-line resonance centered at 4.82 ppm (C,-H, trans, 1 H ) .…”

Conformational analysis of cyclic tetrapeptides by molecular mechanics calculations

“…(15) calculated the conformational energy of cyclo-Gly, by the molecular mechanics methods and concluded that the conformation with i, symmetry is more stable than the one with i? (15) calculated the conformational energy of cyclo-Gly, by the molecular mechanics methods and concluded that the conformation with i, symmetry is more stable than the one with i?…”