Oxyazapeptides: Synthesis, Structure Determination, and Conformational Analysis

Herein we report the synthesis, X-ray
structure determination,
and conformational analysis of a novel class of heteroatom-modified
peptidomimetics, which we shall call “oxyazapeptides”.
Substituting the typical native N-Cα bond with an
O-Nα bond creates a completely new, previously unknown
family of peptidomimetics, which are hydrolytically stable and display
very interesting conformational behavior. Force field calculations
revealed that the barrier to rotation around the O-Nα bond in oxyazapeptides is five times lower than that around the
N-Nα bond in azapeptides. Also, conformational analysis
supported by X-ray suggests that the oxyaza moiety can effectively
induce β-turns, which can make the newly discovered oxyazapeptide
scaffold a useful tool for drug discovery and for design of biologics.