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Enzymatic Fluoromethylation as a Tool for ATP-Independent Ligation.

ABSTRACT: S-adenosylmethionine-dependent methyltransferases are involved in countless biological processes, including signal transduction, epigenetics, natural product biosynthesis, and detoxification. Only a handful of carboxylate methyltransferases have evolved to participate in amide bond formation. In this report we show that enzyme-catalyzed F-methylation of carboxylate substrates produces F-methyl esters that readily react with N- or S-nucleophiles under physiological conditions. We demonstrate the applicability of this approach to the synthesis of small amides, hydroxamates, and thioesters, as well as to site-specific protein modification and native chemical ligation.

SUBMITTER: Peng J

PROVIDER: S-EPMC10952888 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Enzymatic Fluoromethylation as a Tool for ATP-Independent Ligation.

Peng Jiaming J Hughes Gregory R GR Müller Manuel M MM Seebeck Florian P FP

Angewandte Chemie (International ed. in English) 20231129 1

S-adenosylmethionine-dependent methyltransferases are involved in countless biological processes, including signal transduction, epigenetics, natural product biosynthesis, and detoxification. Only a handful of carboxylate methyltransferases have evolved to participate in amide bond formation. In this report we show that enzyme-catalyzed F-methylation of carboxylate substrates produces F-methyl esters that readily react with N- or S-nucleophiles under physiological conditions. We demonstrate the ...[more]

PMID: 37955592

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