Open AccessSynthesis of S ‐Adenosyl‐L‐Methionine Analogs with Extended Transferable Groups for Methyltransferase‐Directed Labeling of DNA and RNA
Author(s) -
Masevičius Viktoras,
Nainytė Milda,
Klimašauskas Saulius
Publication year - 2016
Publication title -
current protocols in nucleic acid chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.306
H-Index - 17
eISSN - 1934-9289
pISSN - 1934-9270
DOI - 10.1002/0471142700.nc0136s64
Subject(s) - methyltransferase , chemistry , sulfonium , methylation , stereochemistry , alkylation , dna , rna , amine gas treating , methionine , azide , methyl group , cofactor , combinatorial chemistry , biochemistry , enzyme , group (periodic table) , catalysis , organic chemistry , amino acid , gene , salt (chemistry)
Abstract S ‐Adenosyl‐L‐methionine (AdoMet) is a ubiquitous methyl donor for a variety of biological methylation reactions catalyzed by methyltransferases (MTases). AdoMet analogs with extended propargylic chains replacing the sulfonium‐bound methyl group can serve as surrogate cofactors for many DNA and RNA MTases enabling covalent deposition of these linear chains to their cognate targets sites in DNA or RNA. Here we describe synthetic procedures for the preparation of two representative examples of AdoMet analogs with a transferable hex‐2‐ynyl group carrying a terminal azide or amine functionality. Our approach is based on direct chemoselective alkylation of S‐adenosyl‐L‐homocysteine at sulfur with corresponding nosylates under acidic conditions. We also describe synthetic routes to 6‐substituted hex‐2‐yn‐1‐ols and their conversion to the corresponding nosylates. Using these protocols, synthetic AdoMet analogs can be prepared within 1 to 2 weeks. © 2016 by John Wiley & Sons, Inc.