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 derivatization and subsequent labeling of their cognate target sites in DNA or RNA. Although AdoMet analogs with saturated aliphatic chains are less popular than propargylic ones, they can be useful for dedicated studies that require certain chemical derivatization. Here we describe synthetic procedures for the preparation of two AdoMet analogs, one with a transferable 6-azidohex-2-ynyl group (carrying an activating C≡C triple bond and a terminal azide functionality), and the other one with a transferable ethyl-2,2,2-d3 group (an isotope-labeled aliphatic moiety). Our synthetic approach is based on direct chemoselective alkylation of S-adenosyl-L-homocysteine at sulfur with a corresponding nosylate or triflate, respectively, under acidic conditions. We also describe synthetic routes to 6-azidohex-2-yn-1-ol and conversion of the alcohols to corresponding nosylate and triflate alkylators. Using these protocols, the synthetic AdoMet analogs can be prepared within 1 to 2 weeks. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of 6-azidohex-2-yn-1-ol Basic Protocol 2: Synthesis of 4-nitrobenzenesulfonate Basic Protocol 3: Synthesis of trifluoromethanesulfonates Basic Protocol 4: S-Alkylation of AdoHcy with sulfonates Basic Protocol 5: Purification and characterization of AdoMet analogs.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.