Department of Chemistry, Institute of Biochemistry, University of Muenster, Wilhelm-Klemm-Straße 2, D-48149 Muenster, Germany.
Chem Commun (Camb). 2020 Feb 18;56(14):2115-2118. doi: 10.1039/c9cc07807j. Epub 2020 Jan 23.
Methyltransferases (MTases) modify a wide range of biomolecules using S-adenosyl-l-methionine (AdoMet) as the cosubstrate. Synthetic AdoMet analogues are powerful tools to site-specifically introduce a variety of functional groups and exhibit potential to be converted only by distinct MTases. Extending the size of the substituent at the sulfur/selenium atom provides selectivity among MTases but is insufficient to discriminate between promiscuous MTases. We present a panel of AdoMet analogues differing in the nucleoside moiety (NM-AdoMets). These NM-AdoMets were efficiently produced by a previously uncharacterized methionine adenosyltransferase (MAT) from methionine and ATP analogues, such as ITP and N-propargyl-ATP. The N-modification changed the relative activity of three representative MTases up to 13-fold resulting in discrimination of substrates for the methyl transfer and could also be combined with transfer of allyl and propargyl groups.
甲基转移酶（MTases）使用 S-腺苷甲硫氨酸（AdoMet）作为共底物修饰多种生物分子。合成的 AdoMet 类似物是一种强大的工具，可以特异性地引入各种官能团，并有可能仅被特定的 MTases 转化。增加硫/硒原子上取代基的大小可以在 MTases 之间提供选择性，但不足以区分混杂的 MTases。我们提供了一组在核苷部分（NM-AdoMets）不同的 AdoMet 类似物。这些 NM-AdoMets 可以通过以前未被表征的蛋氨酸腺苷转移酶（MAT）从蛋氨酸和 ATP 类似物（如 ITP 和 N-炔丙基-ATP）高效地产生。N 修饰改变了三种代表性 MTases 的相对活性高达 13 倍，从而区分了甲基转移的底物，并可以与烯丙基和炔丙基基团的转移结合使用。
