5135-39-7Relevant articles and documents
S-ADENOSYL-L-CYSTEINE ANALOGUES AS COFACTORS FOR METHYLTRANSFERASES
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Page/Page column 41; 42, (2016/03/22)
Cofactor analogues for methyltransferases are disclosed. The compounds are represented by formula (I) wherein R1 is COOH or COO-; X is an organic or inorganic anion carrying one or more negative charges; Y and Y' are H, or an alkyl; R2 is NH2, NHBoc, or H; and Z is S or Se. R comprises a carbon-carbon double bond, carbon-oxygen double bond, carbon-sulfur double bond, carbon-nitrogen double bond, a carbon-carbon triple bond, carbon-nitrogen triple bond, an aromatic carbocyclic or heterocyclic system in β-position to the sulfonium center, unsaturated c-c bond, or c-heteroatom bond where the heteroatom is O, N, S.
Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L
Anglin, Justin L.,Deng, Lisheng,Yao, Yuan,Cai, Guobin,Liu, Zhen,Jiang, Hong,Cheng, Gang,Chen, Pinhong,Song, Yongcheng,Dong, Shuo
supporting information, p. 8066 - 8074,9 (2020/09/15)
Histone3-lysine79 (H3K79) methyltransferase DOT1L has been found to be a drug target for acute leukemia with MLL (mixed lineage leukemia) gene translocations. A total of 55 adenosine-containing compounds were designed and synthesized, among which several potent DOT1L inhibitors were identified with Ki values as low as 0.5 nM. These compounds also show high selectivity (>4500-fold) over three other histone methyltransferases. Structure-activity relationships (SAR) of these compounds for their inhibitory activities against DOT1L are discussed. Potent DOT1L inhibitors exhibit selective activity against the proliferation of MLL-translocated leukemia cell lines MV4;11 and THP1 with EC50 values of 4-11 μM. Isothermal titration calorimetry studies showed that two representative inhibitors bind with a high affinity to the DOT1L:nucleosome complex and only compete with the enzyme cofactor SAM (S-adenosyl-l-methionine) but not the substrate nucleosome.
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).
