Synthesis of selenocysteine-containing dipeptides modeling the active site of thioredoxin reductase

Abstract

Four cyclic dipeptides modeling the active site of thioredoxin reductase (TrxR), UU, CU, UC, and CC, where U and C represent selenocystine and cystine, respectively, were synthesized and their glutathione peroxidase (GPx)-like catalytic activity was evaluated by the reaction of hydrogen peroxide (H₂O₂) with glutathione (GSH) in the presence of glutathione reductase (GR). Among these, only UC exhibited the significant antioxidant capacity, suggesting that an atomic environment around the Se–S bond is relevant to the reactivity toward a thiol substrate.

GRAPHICAL ABSTRACT

Keywords:

• Selenopeptide
• selenenyl sulfide
• TrxR mimics
• NH···Se hydrogen bond

Acknowledgments

We thank K. Katsumata for assistance of the synthesis of 1-4.

Additional information

Funding

This work was supported by JSPS KAKENHI Grant Number JP17K05792 (M. I.).