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Selenomethionine as an expressible handle for bioconjugations.


ABSTRACT: Site-selective chemical bioconjugation reactions are enabling tools for the chemical biologist. Guided by a careful study of the selenomethionine (SeM) benzylation, we have refined the reaction to meet the requirements of practical protein bioconjugation. SeM is readily introduced through auxotrophic expression and exhibits unique nucleophilic properties that allow it to be selectively modified even in the presence of cysteine. The resulting benzylselenonium adduct is stable at physiological pH, is selectively labile to glutathione, and embodies a broadly tunable cleavage profile. Specifically, a 4-bromomethylphenylacetyl (BrMePAA) linker has been applied for efficient conjugation of complex organic molecules to SeM-containing proteins. This expansion of the bioconjugation toolkit has broad potential in the development of chemically enhanced proteins.

SUBMITTER: Flood DT 

PROVIDER: S-EPMC7923357 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Selenomethionine as an expressible handle for bioconjugations.

Flood Dillon T DT   Hintzen Jordi C J JCJ   Knouse Kyle W KW   Hill David E DE   Lu Chenxi C   Cistrone Philip A PA   Chen Jason S JS   Otomo Takanori T   Dawson Philip E PE  

Proceedings of the National Academy of Sciences of the United States of America 20210201 8


Site-selective chemical bioconjugation reactions are enabling tools for the chemical biologist. Guided by a careful study of the selenomethionine (SeM) benzylation, we have refined the reaction to meet the requirements of practical protein bioconjugation. SeM is readily introduced through auxotrophic expression and exhibits unique nucleophilic properties that allow it to be selectively modified even in the presence of cysteine. The resulting benzylselenonium adduct is stable at physiological pH,  ...[more]

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