Early‐Stage Incorporation Strategy for Regioselective Labeling of Peptides using the 2‐Cyanobenzothiazole/1, 2‐Aminothiol Bioorthogonal Click Reaction. Issue 3 (6th February 2018)

• Record Type: Journal Article
• Authors: Chen, Kuo‐Ting; Ieritano, Christian; Seimbille, Yann
• Is Part Of: ChemistryOpen. Volume 7:Issue 3(2018)
• Page Start: 256
• Page End: 261
• Publication Date: 2018-02-06
• Subjects: biorthogonal chemistry -- click reactions -- fluorescent probes -- peptide modifications -- solid-phase peptide synthesis; Chemistry -- Periodicals; 540; 540.5
• DOI: 10.1002/open.201700191
• Languages: English
• ISSNs: 2191-1363

Abstract

Abstract: 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 dipeptide1 into targeting vectors, such asc[RGDyK(C)] andHER2 pep, during solid‐phase peptide synthesis. Then, the utility of the click reaction to label bioactive peptides with a CBT‐modified imaging agent (FITC–CBT, 9 ) was assessed. The ligation reaction was found to be highly selective and efficient under various conditions. The fluorescently labeled peptides2 and3 were obtained in respective yields of 88 and 82 % under optimized conditions. Abstract : Pep talk : A strategy for directly labeling peptides is described by using a 2‐cyanobenzothiazole (CBT)/1, 2‐aminothiol click reaction. Two peptides are modified with a clickable amino acid during the synthesis by using Fmoc solid‐phase peptide synthesis. The following conjugation with a CBT‐bearing fluorophore is demonstrated to be rapid and chemoselective under various conditions. This synthetic strategy is anticipated to be a useful tool in the development of new peptide‐based imaging probes for biomedical applications.