Genetically Encoded Epoxide Warhead for Precise and Versatile Covalent Targeting of Proteins.

ABSTRACT: Genetically encoding a proximal reactive warhead into the protein binder/drug has emerged as an efficient strategy for covalently binding to protein targets, enabling broad applications. To expand the reactivity scope for targeting the diverse natural residues under physiological conditions, the development of a genetically encoded reactive warhead with excellent stability and broad reactivity is highly desired. Herein, we reported the genetic encoding of epoxide-containing tyrosine (EPOY) for developing covalent protein drugs. Our study demonstrates that EPOY, when incorporated into a nanobody (KN035), can cross-link with different side chains (mutations) at the same position of PD-L1 protein. Significantly, a single genetically encoded reactive warhead that is capable of covalent and sit

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11177858 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature