1. Organophosphorus S -adenosyl- L -methionine mimetics: synthesis, stability, and substrate properties.
- Author
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Rudenko AY, Mariasina SS, Bolikhova AK, Nikulin MV, Ozhiganov RM, Vasil'ev VG, Ikhalaynen YA, Khandazhinskaya AL, Khomutov MA, Sergiev PV, Khomutov AR, and Polshakov VI
- Abstract
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-P
H , 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 and incorporating reporter groups into their substrates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rudenko, Mariasina, Bolikhova, Nikulin, Ozhiganov, Vasil’ev, Ikhalaynen, Khandazhinskaya, Khomutov, Sergiev, Khomutov and Polshakov.)- Published
- 2024
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