Solution conformations of two flexible cyclic pentapeptides: cyclo(Gly‐Pro‐D‐Phe‐Gly‐Ala) and cyclo(Gly‐Pro‐D‐Phe‐Gly‐Val)

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Abstract
In an effort to explore the residue preferences in three‐residue reverse turns (so‐called ‐γ‐turns), two cyclic pentapeptides—cyclo(Gly1‐Pro2‐D‐Phe3‐Gly4‐Ala5) (I) and cyclo (Gly1‐Pro2‐D‐Phe3‐Gly4‐Val5) (II)—have been synthesized and analyzed by nmr. It was anticipated that the Gly‐Pro‐D‐Phe‐Gly portions of these molecules would favor a β‐turn conformation, leaving the remainder of the molecule to adopt a γ turn, as seen in several previously studied model cyclic pentapeptides. The nmr data for both peptides in CDCl3 (5% DMSO‐d6) and in neat DMSO‐d6 indicate that the most populated conformation contains a distorted β turn around Pro2‐D‐Phe3, which includes a γ turn around D‐Phe3. The distorsion in the β turn does not impede the formation of an inverse γ turn around residue 5, and indeed, this conformation is observed in both peptides. Both the alanine and the bulkier valine residues are therefore found to be compatible with an inverse γ turn. Molecular dynamics simulations on the title peptides are reported in the following paper. These simulations indicate that there is conformational flexibility around the D‐Phe3‐Gly4 peptide bond, which enables the formation of the γ turn around D‐Phe3. The third paper in this series explores the impact of a micellar environment on conformational equilibria in II. © 1992 John Wiley & Sons, Inc.