title: 2-Methyladenosine-Substituted 2',5'-oligoadenylates: conformations, 2-5A binding and catalytic activities with human ribonuclease L.
abstract: 2-Methyladenosine-substituted analogues of 2-5A, p5'A2'p5'A2'p5'(me2A), p5'(me2A)2'p5'A2'p5'A, and p5'(me2A) 2'p5'(me2A)2'pS'(me2A), were prepared via a modification of a lead ion-catalyzed ligation reaction. These 5'-monophosphates were subsequently converted into the corresponding 5'-triphosphates. Both binding and activation of human recombinant RNase L by various 2-methyladenosine-substituted 2-5A analogues were examined. Among the 2-5A analogues, p5'A2'p5'A2'p5'(me2A) showed the strongest binding affinity and was as effective as 2-5A itself as an activator of RNase L. The CD spectra of both p5'(me2A)2'p5'A2'p5'A and p5'A2'p5'A2'p5'(me2A) were superimposable on that of p5'A2'p5'A2'p5'A, indicative of an anti orientation about the base-glycoside bonds as in naturally occurring 2-5A.
authors.affiliation: Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Japan. kitade@apchem.gifu-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kitade
authors.forename: M
authors.initials: M
authors.lastname: Wakana
authors.forename: T
authors.initials: T
authors.lastname: Tsuboi
authors.forename: C
authors.initials: C
authors.lastname: Yatome
authors.forename: S F
authors.initials: SF
authors.lastname: Bayly
authors.forename: M R
authors.initials: MR
authors.lastname: Player
authors.forename: P F
authors.initials: PF
authors.lastname: Torrence
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002384:Catalysis / Q000187:drug effects; D002942:Circular Dichroism; D004722:Endoribonucleases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D009843:Oligoribonucleotides; D011994:Recombinant Proteins; C031088:2-methyladenosine; D000249:Adenosine Monophosphate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D000241:Adenosine