DEPSIPEPTIDE ANALOGS OF ELASTIN REPEATING SEQUENCES - CONFORMATIONAL-ANALYSIS

In this work the effect of elimination of a specific hydrogen bond on the conformation of the repeating peptides of elastin was studied. These repeating sequences are the pentapeptide Val‐Pro‐Gly‐Val‐Gly and the hexapeptide Val‐Ala‐Pro‐Gly‐Val‐Gly. These sequences have been proposed to occur in a β‐turn conformation with a hydrogen bond involving the amide NH of the internal valine residue and the carbonyl oxygen of the residue preceding proline. In the depsipeptide analogues studied in this work, this 4–1 β‐turn hydrogen bond cannot occur. We studied the depsipeptide sequences Val‐Pro‐Gly‐Hiv‐Gly and Val‐Ala‐Pro‐Gly‐Hiv‐Gly (Hiv denotes S‐α‐hydroxyisovaleric acid, the hydroxy acid analogue of valine), as well as the peptide sequences Val‐Pro‐Gly‐Val‐Gly and Val‐Ala‐Pro‐Gly‐Val‐Gly. Compunds studied included sequences with the Boc and benzyl ester protecting groups, derivatives with the acetyl and N‐methylamide end groups and polymers of the above sequences. Our conclusions are based on a comparison of depsipeptides with analogous peptides. Conformational analysis was carried out by nmr, CD, and ir spectroscopy. We propose that in the repeating sequences of elastin an equilibrium exists between a γ‐turn structure and a β‐turn structure in the Pro‐Gly segment resulting in a structure that combines flexibility with strong conformational preferences. The C7 involves the amide NH of the internal glycine and the carbonyl oxygen of the residue preceding proline. In the N‐methylamide derivatives a similar equilibrium exists in the Gly‐Val‐Gly segment. In the depsipeptides the β‐turn cannot occur and only the γ‐turn is seen. In the polydepsipeptides the major conformational feature is a type I β‐turn involving Gly5 NH and Pro CO. Copyright © 1990 John Wiley & Sons, Inc.