35899-54-8Relevant academic research and scientific papers
Facile chemoenzymatic strategies for the synthesis and utilization of S-adenosyl-L-methionine analogues
Singh, Shanteri,Zhang, Jianjun,Huber, Tyler D.,Sunkara, Manjula,Hurley, Katherine,Goff, Randal D.,Wang, Guojun,Zhang, Wen,Liu, Chunming,Rohr, Juergen,Van Lanen, Steven G.,Morris, Andrew J.,Thorson, Jon S.
supporting information, p. 3965 - 3969 (2014/05/06)
A chemoenzymatic platform for the synthesis of S-adenosyl-L-methionine (SAM) analogues compatible with downstream SAM-utilizing enzymes is reported. Forty-four non-native S/Se-alkylated Met analogues were synthesized and applied to probing the substrate specificity of five diverse methionine adenosyltransferases (MATs). Human MAT II was among the most permissive of the MATs analyzed and enabled the chemoenzymatic synthesis of 29 non-native SAM analogues. As a proof of concept for the feasibility of natural product alkylrandomization , a small set of differentially-alkylated indolocarbazole analogues was generated by using a coupled hMAT2-RebM system (RebM is the sugar C4′-O-methyltransferase that is involved in rebeccamycin biosynthesis). The ability to couple SAM synthesis and utilization in a single vessel circumvents issues associated with the rapid decomposition of SAM analogues and thereby opens the door for the further interrogation of a wide range of SAM utilizing enzymes. Mix and MATch: Methionine adenosyltransferase (MAT) was used to synthesize S-adenosylmethionine (SAM) analogues in a method directly compatible with downstream SAM-utilizing enzymes. As a proof of concept for the feasibility of natural product alkylrandomization by using this method, a coupled strategy in which MAT was applied in conjunction with the methyltransferase RebM was used to generate a small set of indolocarbazole analogues.
Design, synthesis, and biological evaluation of novel human 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP) substrates
Kung, Pei-Pei,Zehnder, Luke R.,Meng, Jerry J.,Kupchinsky, Stanley W.,Skalitzky, Donald J.,Johnson, M. Catherine,Maegley, Karen A.,Ekker, Anne,Kuhn, Leslie A.,Rose, Peter W.,Bloom, Laura A.
, p. 2829 - 2833 (2007/10/03)
The structure-based design, chemical synthesis, and biological evaluation of novel MTAP substrates are described. These compounds incorporate various C5′-moieties and are shown to have different kcat/Km values compared with the natural MTAP substrate (MTA).
