8-Methyladenosine-substituted analogues of 2-5A: synthesis and their biological activities.
8-Methyladenosine-substituted analogues of 2-5A, p5'A2'p5'A2'p5'(me8A), p5'A2'p5'(me8A)2'p5'(me8A), p5'(me8A)2'p5'(me8A)2'p5'(me8A), and p5'(me8A) 2'p5'A2'p5'A, were prepared via a modification of a lead ion-catalyzed ligation reaction. These 2-5A monophosphates were converted into the corresponding 5'-triphosphates. Substitution of an 8-methyladenosine residue at the third position (2'-terminus) of the oligonucleotides increased the stability to snake venom phosphodiesterase digestion. Both binding and activation of mouse liver 2-5A dependent ribonuclease (RNase L) by the various 8-methyladenosine-substituted 2-5A analogues were examined. Among the 8-methyladenosine-substituted trimer analogues, the analogues with 8-methyladenosine residing in the 2'-terminal position showed the strongest binding affinity and were several times more effective than 2-5A itself as an inhibitor of translation.
Kitade
Y
Y
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Japan.
Nakata
Y
Y
Hirota
K
K
Maki
Y
Y
Pabuccuoglu
A
A
Torrence
P F
PF
D000227:Adenine Nucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D004722:Endoribonucleases / Q000378:metabolism; D007700:Kinetics; D008110:Liver Extracts; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D012313:RNA / Q000378:metabolism*; D051381:Rats
D000227:Adenine Nucleotides; D008110:Liver Extracts; D009843:Oligoribonucleotides; C070330:8-methyladenosine; C023505:2',5'-oligoadenylate; D012313:RNA; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom; D000241:Adenosine