Synthesis of S-adenosyl-L-methionine analogs and their use for sequence-specific transalkylation of DNA by methyltransferases
- 22 November 2006
- journal article
- Published by Springer Nature in Nature Protocols
- Vol. 1 (4), 1879-1886
- https://doi.org/10.1038/nprot.2006.253
Abstract
Here we describe a one-step synthetic procedure for the preparation of S-adenosyl-L-methionine (AdoMet) analogs with extended carbon chains replacing the methyl group. These AdoMet analogs function as efficient cofactors for DNA methyltransferases (MTases), and we provide a protocol for sequence-specific transfer of extended side chains from these AdoMet analogs to DNA by DNA MTases. Direct chemoselective allylation or propargylation of S-adenosyl-L-homocysteine (AdoHcy) at sulfur is achieved under the acidic conditions needed to protect other nucleophilic positions in AdoHcy. The unsaturated bonds in beta position to the sulfonium center of the resulting AdoMet analogs are designed to stabilize the transition state formed upon DNA MTase-catalyzed nucleophilic attack at the carbon next to the sulfonium center and lead to efficient transfer of the extended side chains to DNA. Using these protocols, sequence-specific functionalized DNA can be obtained within one to two weeks.Keywords
This publication has 18 references indexed in Scilit:
- Direct transfer of extended groups from synthetic cofactors by DNA methyltransferasesNature Chemical Biology, 2005
- A straightforward preparation of primary alkyl triflates and their utility in the synthesis of derivatives of ethidiumJournal of the Chemical Society, Perkin Transactions 1, 2000
- S-Adenosylmethionine-Dependent MethyltransferasesPublished by World Scientific Pub Co Pte Ltd ,1999
- A self-cleaving DNA nucleosideChemical Communications, 1997
- S‐Adenosylmetliionine and methylationThe FASEB Journal, 1996
- A novel sensitive and specific assay for abasic sites, the most commonly produced DNA lesionBiochemistry, 1992
- Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 5. Role of the asymmetric sulfonium pole in the enzymic binding of S-adenosyl-L-methionineJournal of Medicinal Chemistry, 1976
- The S-n-propyl analogue of S-adenosylmethionineBiochimica et Biophysica Acta (BBA) - General Subjects, 1975
- S-Adenosylmethionine: The Relation of Configuration at the Sulfonium Center to Enzymatic Reactivity1Journal of the American Chemical Society, 1959
- THE NATURE OF THE ACTIVE METHYL DONOR FORMED ENZYMATICALLY FROM L-METHIONINE AND ADENOSINETRIPHOSPHATE1,2Journal of the American Chemical Society, 1952