Peptide conformation

Abstract

Six cyclic retro‐analogues of the peptide hormone somatostatin have been synthesized using the solid phase technique. The peptides cyclo(‐Xaa1‐Phe2‐Thr3‐Lys4‐Ybb5‐Phe6‐) and cyclo(‐Phe1‐Xaa2‐Thr3‐Lys4‐Ybb5‐Phe6‐) with Xaa =d‐ or l‐Pro and Ybb =d‐ or l‐Trp were cyclized via the azide method. The conformations of the cyclic hexapeptides in DMSO‐d6 solution were determined by a number of homo‐ and heteronuclear two‐dimensional n.m.r.‐techniques including 2D rotating frame NOE‐spectroscopy. Two‐step coherence transfers, ROE and chemical exchange, are observed for the first time in ROESY spectra. The backbone conformation of the all‐trans cyclopeptides consists of a β‐turn containing the Pro residue in the position i + 1. These retro‐analogues of somatostatin exhibit a high activity in the inhibition of cholate and phalloidin uptake by liver cells (cytoprotective effect); however, the hormonal activities of the natural hormone are completely suppressed. The constitutional and conformational requirements for the cytoprotective activity are discussed.

Synthesis, conformational studies, and molecular dynamics calculations of two cyclic tetrapeptides with 17‐ and 18‐membered rings

“…The assignment of the major conformer is straightforward in both cases from the H,H-COSY spectrum (28). To assign the minor conformer, the ROESY experiment (29)(30)(31) was the most useful, because it can discriminate between cross-relaxation by dipolar interaction and chemical exchange (32,33). In a phase sensitive ROESY spectrum the cross peaks originating from chemical exchange are positive like the diagonal peaks whereas the ROES have opposite signs.…”