Cystine peptides: the intramolecular antiparallel beta-sheet conformation of a 20-membered cyclic peptide disulfide.

Abstract

AbstractA 20‐membered cyclic peptide disulfide magnified image has been synthesized as a conformational model for disulfide loops of limited ring size. 1H‐nmr studies at 270 MHz establish the presence of three intramolecular hydrogen bonds involving the Leu, Val, and methylamide NH groups in CDCl3. Evidence for peptide aggregation in CDCl3 is also presented. A structural transition involving loosening of the hydrogen bond formed by the Val NH group is observed upon the measured addition of (CD3)2SO to CDCl3. Hydrogen‐bonding studies, together with unusually low field positions of the Cys(1) and Cys(6) CαH resonances and high J values provide support for an intramolecular antiparallel β‐sheet conformation, facilitated by a chain reversal at the Aib‐Ala segment. Extensive nuclear Overhauser effect studies provide compelling evidence for the proposed conformation and also establish a type I′ β‐turn at the Aib‐Ala residues, the site of the chain reversal.