Organophosphorus S-adenosyl-L-methionine mimetics: synthesis, stability, and substrate properties

Rudenko, A.Y.; Mariasina, S.S.; Bolikhova, A.K.; Nikulin, M.V.; Ozhiganov, R.M.; Vasil’ev, V.G.; Ikhalaynen, Y.A.; Khandazhinskaya, A.L.; Khomutov, M.A.; Sergiev, P.V.; Khomutov, A.R.; Polshakov, V.I.

Авторы: Rudenko A.Y., Mariasina S.S., Bolikhova A.K., Nikulin M.V., Ozhiganov R.M., Vasil’ev V.G., Ikhalaynen Y.A., Khandazhinskaya A.L., Khomutov M.A., Sergiev P.V., Khomutov A.R., Polshakov V.I.
Журнал: Frontiers in Chemistry
Том: 12
Год издания: 2024
Первая страница: 01
Последняя страница: 16
Номер статьи: 1448747
DOI: 10.3389/fchem.2024.1448747
Аннотация: S-Adenosyl-L-methionine (SAM)-mediated methylation of biomolecules controls their function and regulates numerous vital intracellular processes. Analogs of SAM with a reporter group in place of the S-methyl group are widely used to study these processes. However, many of these analogs are chemically unstable that largely limits their practical application. We have developed a new compound, SAM-PH, which contains an H-phosphinic group (-P(O)(H)OH) instead of the SAM carboxylic group. SAM-PH is significantly more stable than SAM, retains functional activity in catechol-O-methyltransferase and methyltransferase WBSCR27 reactions. The last is associated with Williams–Beuren syndrome. Rac-SAM-PH was synthesized chemically, while (R,S)-SAM-PH and its analogs were prepared enzymatically either from H-phosphinic analogs of methionine (Met-PH) or H-phosphinic analog of S-adenosyl-L-homocysteine (SAH-PH) using methionine adenosyltransferase 2A or halide methyltransferases, respectively. SAH-PH undergoes glycoside bond cleavage in the presence of methylthioadenosine nucleosidase like natural SAH. Thus, SAM-PH and its analogs are promising new tools for investigating methyltransferases andincorporating reporter groups into their substrates.
Добавил в систему: Польшаков Владимир Иванович

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Organophosphorus S-adenosyl-L-methionine mimetics: synthesis, stability, and substrate propertiesстатья Исследовательская статья

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