Synthesis of 2',5'-oligoadenylate analogs containing an adenine acyclonucleoside and their ability to activate human RNase L.
This paper described synthesis of 2',5'-oligoadenylate (2-5A) analogs containing the purine acyclonucleoside, 9-[(2'S,3'R)-2',3',4'-trihydroxybutyl]adenine (2). The ability of the analogs to activate recombinant human RNase L was evaluated using 5'-32P-r(C11U2C7)-3' as a substrate. The EC50 value (the concentration of the 2-5A required to cleave half of the RNA) of the parent 2-5A tetramer 13 was 1.0 nM, whereas those of the analog 14 incorporating 2 at the second position from the 5'-end and the analog 15 incorporating 2 at the third position from the 5'-end were 9.0 and 1.7 nM, respectively. The analogs 14 and 15 were only 9- and 1.7-fold less potent than the parent 2-5A 13 itself, in RNase L activation ability. Furthermore, the oligodeoxynucleotide containing 2 was more resistant to nucleolytic hydrolysis by snake venom phosphodiesterase (a 3'-exonuclease) than the unmodified oligodeoxynucleotide. Thus, incorporation of an acyclonucleoside into 2-5A may be useful for developing an antiviral agent based on the 2-5A system.
Ueno
Yoshihito
Y
Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, 501-1193, Japan.
Ishihara
Shinji
S
Ito
Yasutomo
Y
Kitade
Yukio
Y
D000225:Adenine / Q000138:chemical synthesis* / Q000378:metabolism; D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis* / Q000378:metabolism; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D000227:Adenine Nucleotides; D009705:Nucleosides; D009843:Oligoribonucleotides; D011994:Recombinant Proteins; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D000225:Adenine