UNIT 1.36 Synthesis of S‐Adenosyl‐L‐Methionine Analogs with Extended Transferable Groups for Methyltransferase‐Directed Labeling of DNA and RNA. Issue 1 (1st March 2016)

• Record Type: Journal Article
• Authors: Masevičius, Viktoras; Nainytė, Milda; Klimašauskas, Saulius
• Is Part Of: Current protocols in nucleic acid chemistry. Volume 64:Issue 1(2016)
• Page Start: 1.36.1
• Page End: 1.36.13
• Publication Date: 2016-03-01
• Subjects: methyltransferase -- cofactor engineering -- synthetic AdoMet analogs -- mTAG labeling -- S‐selective alkylation; Nucleic acids -- Laboratory manuals; Nucleic Acids -- chemical synthesis; Nucleic acids; Laboratory Manuals; Electronic books; Laboratory manuals; 572.8028
• DOI: 10.1002/0471142700.nc0136s64
• Languages: English
• ISSNs: 1934-9270

Abstract

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.