Early-Stage Incorporation Strategy for Regioselective Labeling of Peptides using the 2-Cyanobenzothiazole/1,2-Aminothiol Bioorthogonal Click Reaction.

Herein, we describe a synthetic strategy for the regioselective labeling of peptides by using a bioorthogonal click reaction between 2-cyanobenzothiazole (CBT) and a 1,2-aminothiol moiety. This methodology allows for the facile and site-specific modification of peptides with various imaging agents, including fluorophores and radioisotope-containing prosthetic groups. We investigated the feasibility of an early-stage incorporation of dipeptide into targeting vectors, such as and , during solid-phase peptide synthesis. Then, the utility of the click reaction to label bioactive peptides with a CBT-modified imaging agent (FITC-CBT, ) was assessed. The ligation reaction was found to be highly selective and efficient under various conditions. The fluorescently labeled peptides and were obtained in respective yields of 88 and 82 % under optimized conditions.