Conformation of diastereomeric peptide sequences: Structural analysis of Z‐D‐Val‐Ac6c‐Gly‐L‐Phe‐OMe

We have recently undertaken a systematic structural analysis of fully protected tetrapeptides containing at the N‐ and C‐terminus either homo‐ or heterochiral amino acids, spaced by an achiral dipeptide segment. The interest for this class of peptides derives from the observation that, on reverse‐phase (HPLC), the homo‐ and heterochiral sequences have a markedly different retention times. The diastereomeric sequences, namely Z‐(L/D)‐Val‐X‐Y‐L‐Phe‐OMe (X = Sar, Gly, Ac3c, Aib, Ac5c, Ac6c, Deg, Dpg, Dbu, Dip, Dph; Y = Sar, Gly, Ac3c, Aib, Ac6c, Ac6c) show different overall hydrophobicity attributed to a different three‐dimensional structure that also depends on the X‐Y segment. Therefore, following preliminary studies in solution, we report here the detailed x‐ray analysis of the tetrapeptide Z‐D‐Val‐Ac6c‐Gly‐L‐Phe‐OMe in order to understand the structural features governing the overall hydrophobicity of linear fully protected tetrapeptides. © 1992 John Wiley & Sons, Inc. Copyright © 1992 John Wiley & Sons, Inc.