3,4-Dihydroquinolizinium Ring, the Core Structure of Quinocidin, as a Cysteine-Selective Electrophile.

Abstract

Quinocidin is an actinomycete-derived natural product with an unusual 3,4-dihydroquinolizinium (DQ) ring, which reacts with thiols via a Michael addition-type reaction. In view of the simple structure and reactivity toward thiols, the DQ ring has the possibility to become a unique electrophile toward cysteine (Cys) for use in biochemical research. Herein, this possibility is investigated by evaluating the reactivity of a simple DQ salt toward amino acids and Cys-containing peptides in neutral aqueous media. The results show that the DQ salt selectively forms adducts with free Cys and Cys residues in peptides. It is also demonstrated that the DQ salt effectively inhibits the enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase, which contains a Cys residue in its active center. These results indicate that the DQ ring could serve as a new reactive group capable of Cys modification for biochemical and pharmaceutical applications.