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Updated: Nov 6, 2025

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay
Published on: February 28, 2025
Direct screening of a target-specific covalent binder: stringent regulation of warhead reactivity in a matchmaking
Yudai Tabuchi1, Takahito Watanabe1, Riku Katsuki1
1Department 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.
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.
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