Direct screening of a target-specific covalent binder: stringent regulation of warhead reactivity in a matchmaking environment

Yudai Tabuchi; Takahito Watanabe; Riku Katsuki; Yuji Ito; Masumi Taki

doi:10.1039/d1cc01773j

Direct screening of a target-specific covalent binder: stringent regulation of warhead reactivity in a matchmaking environment

Chem Commun (Camb). 2021 Jun 1;57(44):5378-5381. doi: 10.1039/d1cc01773j.

Authors

Yudai Tabuchi¹, Takahito Watanabe¹, Riku Katsuki¹, Yuji Ito², Masumi Taki¹

Affiliations

¹ Department of Engineering Science, Bioscience and Technology Program, The Graduate School of Informatics and Engineering, The University of Electro-Communications (UEC), 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan. taki@pc.uec.ac.jp.
² Department of Chemistry and Bioscience, Graduate School of Science and Engineering, Kagoshima University, 1-21-35 Korimoto, Kagoshima, Kagoshima 890-0065, Japan.

PMID: 33978001
DOI: 10.1039/d1cc01773j

Abstract

A peptide-type covalent binder for a target protein was obtained by direct and stringent screening of a warhead-modified peptide library on the robust T7 phage. The aryl fluorosulfate (fosylate) warhead was activated only in a matchmaking microenvironment created between the target protein and an appropriate peptide during the reactivity/affinity-based co-selection process of extended phage display.