Synthesis of SAM-Adenosine Conjugates for the Study of m6A-RNA Methyltransferases

被引：11

作者：

Atdjian, Colette ^{[1
]}

Iannazzo, Laura ^{[1
]}

Braud, Emmanuelle ^{[1
]}

Etheve-Quelquejeu, Melanie ^{[1
]}

机构：

[1] Univ Paris 05, UMR 8601, Lab Chim & Biochim Pharmacol & Toxicol, Team Chem RNAs Nucleosides Peptides & Heterocycle, F-75005 Paris, France

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2018年 / 2018卷 / 32期

关键词：

S-adenosyl-l-methionine; Bisubstrate; M(6)A modification; RNA methyltransferase; Nucleosides chemistry; BISUBSTRATE INHIBITORS; N-METHYLTRANSFERASE; MULTISUBSTRATE ADDUCTS; DNA METHYLTRANSFERASE; NUCLEOSIDE ANALOGS; FACILE SYNTHESIS; ANTICODON STEM; RNA; METHYLATION; DESIGN;

D O I：

10.1002/ejoc.201800798

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

RNA methyltransferases (RNMTs) catalyze the methylation of RNA using S-adenosyl-l-methionine (SAM) as the methyl donor. Methylation at the N-6 position of adenosine is the most abundant modification found in nearly all classes of RNAs and contributes to the regulation of many biological processes in the three domains of life. However, this family of enzymes remains relatively unexplored by the medicinal chemistry community and new molecules are needed for their studies. Since RNMTs are suitable for bisubstrate binding, we report here the synthesis of SAM-adenosine conjugates as bisubstrate analogues for RNMTs responsible for methylation of the N6-position of adenosine. Six compounds were synthesized by connecting an analogue of SAM to an adenosine unit chosen to mimic the RNA substrate, via alkyl and urea linkers.

引用

页码：4411 / 4425

页数：15

共 78 条

[41] Palladium-catalyzed C-N and C-C cross-couplings as versatile, new avenues for modifications of purine 2'-deoxynucleosides [J].