Accessing the disallowed conformations of peptides employing amide-to-imidate modification0

摘要

Selective modification of the C-terminal amide in peptides to dihydrooxazine (a novel stable imidate isostere) by intramolecular nucleophilic cyclo-O-alkylation of the corresponding A-(3-bromopropyl)amides results in constraining of the C-terminal residue in natively disallowed conformations both in crystals and in solution. The range of disallowed dihedral angles (φ, ψ) for residues in peptides is governed by their local steric and electrostatic clashes.1 Rare tolerances of violations in these angles2 are attributed to distortions in both local and global bond characteristics of the peptides.