Susanna K. Elledge, Hai L. Tran, Alec H. Christian, Veronica Steri, Byron Hann, F. Dean Toste, Christopher J. Chang, James A. Wells
Proceedings of the National Academy of Sciences 2020
Site-specific chemical modification of proteins remains a critical need for bioconjugation. Here we explore the key parameters needed for efficient, selective, and stable modification of methionine using recently developed oxaziridine reagents, called ReACT. We systematically tested various oxaziridine compounds, and scanned accessible and buried sites in a therapeutic antibody for breast cancer to determine the chemical and structural parameters for most stable and efficient modification. We show these adducts are highly stable over days and can support the delivery of toxic payloads to regress tumors in animals. These studies on this important chemical modification expand our capability to site-specifically modify proteins and antibodies for many applications.
A blog highlighting recent publications in the area of covalent modification of proteins, particularly relating to covalent-modifier drugs. @CovalentMod on Twitter and @email@example.com on Mastodon
Monday, March 2, 2020
Systematic identification of engineered methionines and oxaziridines for efficient, stable, and site-specific antibody bioconjugation [@Toste_Group, @christhechang
Covalent drug discovery using sulfur(VI) fluoride exchange warheads
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