Synthesis of DNA Dumbbell Based Inhibitors for the Human DNA Methyltransferase Dnmt1

Angewandte Chemie, 2008, 47, 1515-18 published on 18.01.2008
www.angewandte.org, online article
DNA methyltransferases convert deoxycytidine (dC) nucleobases in DNA into 5-methyldeoxycytidines (dCMe) using the cofactor S-adenosylmethionine (SAM) as the methyl group donor.Methylation of the canonical dC base, particularly in gene promoter regions, induces complex processes, which finally lead to the silencing of the corresponding gene. This epigenetic gene silencing is of paramount importance for cellular differentiation.Altered methylation patterns and corresponding changes in gene expression are found in practically all tumor cells. The major DNA methyltransferase Dnmt1 is a 183-kDa-large protein that preferentially methylates dC bases in hemimethylated d(CpG) sequences after DNA replication.

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