Synthesis, Redox and Structural Properties of Cystine-Cyclopeptides Containing the Active-Site of the Thioredoxin Superfamily

Abstract

Thioredoxin (TRX), thioredoxin-reductase (TRR), protein disulfide isomerase (POI) and glutaredoxin (GRX) belong to the TRX family of thiol-disulfide oxidoreductases (l]. The active-site sequence motif common to all members of this family is Cys-Xaa-Yaa-Cys. POI is the strongest ,oxidant of the family (Eo = -0.110 V) and is known to be involved in in vivo oxidative folding of proteins. In vitro it catalyzes the refolding of reduced or scrambled RNase A (2). In the present study, !the structural and redox properties of related, conformationally restricted synthetic active-site fragments were investigated, and their ability to act as POI-like protein folding catalysts was comparatively analyzed. Results