2-Methyladenosine-Substituted 2',5'-oligoadenylates: conformations, 2-5A binding and catalytic activities with human ribonuclease L.
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.
Kitade
Y
Y
Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Japan. kitade@apchem.gifu-u.ac.jp
Wakana
M
M
Tsuboi
T
T
Yatome
C
C
Bayly
S F
SF
Player
M R
MR
Torrence
P F
PF
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
D009843:Oligoribonucleotides; D011994:Recombinant Proteins; C031088:2-methyladenosine; D000249:Adenosine Monophosphate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D000241:Adenosine