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Organophosphorus S-adenosyl-L-methionine mimetics: synthesis, stability, and substrate properties.
- Source :
-
Frontiers in Chemistry . 2024, p1-16. 16p. - Publication Year :
- 2024
-
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-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 and incorporating reporter groups into their substrates. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 22962646
- Database :
- Academic Search Index
- Journal :
- Frontiers in Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 179079907
- Full Text :
- https://doi.org/10.3389/fchem.2024.1448747