Direct transfer of extended groups from synthetic cofactors by DNA methyltransferases.
S-Adenosyl-L-methionine (AdoMet) is the major methyl donor for biological methylation reactions catalyzed by methyltransferases. We report the first chemical synthesis of AdoMet analogs with extended carbon chains replacing the methyl group and their evaluation as cofactors for all three classes of DNA methyltransferases. Extended groups containing a double or triple bond in the beta position to the sulfonium center were transferred onto DNA in a catalytic and sequence-specific manner, demonstrating a high utility of such synthetic cofactors for targeted functionalization of biopolymers.
Dalhoff
Christian
C
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52056 Aachen, Germany.
Lukinavicius
Grazvydas
G
Klimasăuskas
Saulius
S
Weinhold
Elmar
E
D001665:Binding Sites; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D003067:Coenzymes / Q000138:chemical synthesis*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000145:classification / Q000378:metabolism*; D008938:Mitosis; D008956:Models, Chemical; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013452:Sulfonium Compounds / Q000737:chemistry / Q000378:metabolism
D003067:Coenzymes; D013452:Sulfonium Compounds; D002244:Carbon; D012436:S-Adenosylmethionine; D015254:DNA Modification Methylases