DNA METHYLTRANSFERASE 1 INHIBITORS: DESIGN SYNTHESIS BASED ON TRANSITION STATE STRUCTURE

摘要

DNA methylation is an epigenetic mark that cells use to silence gene expression [1]. It occurs at "CpG sites" grouped in islands and largely located at gene promoter regions. DNA methylation is involved in normal key processes such as: cell cycle, immune response or X-chromosome inactivation. DNA methyltransferases (DNMTs) are the enzymes responsible for DNA methylation in mammalian genome [2]. DNMTs catalyse the formation of 5-methyl-2'-deoxycytidine units within DNA using S-adenosyl-L-methionine (SAM) as the methyl donor (Fig.1).