Synthetic peptide models for the redox-active disulfide loop of glutaredoxin. Conformational studies

Abstract

Two cyclic peptide disulfides have been synthesized as models for the 14-membered redox-active disulfide loop of glutaredoxin. ¹H NMR studies at 270 MHz in chloroform solutions establish a type I β-turn conformation for the Pro-X segment in both peptides, stabilized by a 4→1 hydrogen bond between the Cys(1) CO and Cys(4) NH groups. Nuclear Overhauser effects establish that the aromatic ring in the X = Phe peptide is oriented over the central peptide unit. In dimethyl sulfoxide solutions two conformational species are observed in slow exchange on the NMR time scale, for both peptides. These are assigned to type I and type II β-turn structures with -Pro-Tyr(Phe)- as the corner residues. The structural assignments are based on correlation of NMR parameters with model 14-membered cyclic cystine peptides with Pro-X spacers. Circular dichroism studies based on the -S-S- n-σ^∗ transition suggest a structural change in the disulfide bridge with changing solvent polarity, establishing conformational coupling between the peptide backbone and the disulfide linkage in these systems.