Conversion of DNA methyltransferases into azidonucleosidyl transferases via synthetic cofactors.

ABSTRACT: Aziridine-based cofactor mimics have been synthesized and are shown to undergo methyltransferase-dependent DNA alkylation. Notably, each cofactor mimic possesses an azide functionality, to which can be attached an assortment of unnatural groups following methyltransferase-dependent DNA delivery. DNA duplexes modified with these cofactor mimics are capable of undergoing the Staudinger ligation with phosphines tethered to biological functionalities following enzymatic modification. This methodology provides a new tool by which to selectively modify DNA in a methyltransferase-dependent way. The conversion of biological methyltransferases into azidonucleosidyl transferases demonstrated here also holds tremendous promise as a means of identifying, as yet, unknown substrates of methylation.

SUBMITTER: Comstock LR 

PROVIDER: S-EPMC1067524 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature