title: One-pot modification of 5'-capped RNA based on methionine analogs.
abstract: This paper outlines chemically and enzymatically synthesized S-adenosylmethionine (AdoMet) analogs and their use in the site-specific modification of RNA by methyltransferases, enabling the facile attachment of clickable moieties to the nucleic acid. We then focus on methodological aspects of setting up a methyltransferase-based enzymatic cascade reaction starting from methionine analogs. This strategy is applied to the one-pot modification of the mRNA cap which is subsequently derivatized in copper-free and copper-catalyzed click reactions. We show that high transfer efficiencies to the cap are obtained using Se-propargyl-, hexenynyl- and azido-bearing methionine analogs. By switching to other methyltransferases our one-pot modification approach should be directly applicable to the regiospecific modification of other target molecules including nucleic acids, proteins and small molecules.
authors.affiliation: University of Münster, Department of Chemistry, Institute of Biochemistry, Wilhelm-Klemm-Strasse 2, 48149 Münster, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Muttach
authors.affiliation: University of Münster, Department of Chemistry, Institute of Biochemistry, Wilhelm-Klemm-Strasse 2, 48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003 CiM), University of Münster, Germany. Electronic address: a.rentmeister@uni-muenster.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rentmeister
mesh_terms: D001665:Binding Sites; D057930:Click Chemistry / Q000379:methods*; D008715:Methionine / Q000737:chemistry* / Q000235:genetics; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D012333:RNA, Messenger; D012436:S-Adenosylmethionine; D008715:Methionine; D008780:Methyltransferases
keywords: Click chemistry; Methionine adenosyltransferase; Methionine analogs; Methyltransferase; mRNA