Chemical synthesis and biological activities of analogues of 2',5'-oligoadenylates containing 8-substituted adenosine derivatives.
The synthesis of sequence-specific 2'-5'-oligonucleotides and analogues of 2'-5' linked oligoadenylates containing 8-substituted adenosine derivatives [8-hydroxypropyladenosine (AHPr) and 8-hydroxyadenosine (AOH)] is reported. The reaction of 5'-phosphoroimidazolidate of 8-substituted adenosines under conditions of lead ion catalyst did not give the corresponding 2'-5' oligoadenylates containing pAHPr and pAOH. When these reactions were carried out in the presence of uranyl ion (UO2(2+] in place of lead ion as a catalyst, the desired 2'-5' oligoadenylates were obtained. The p5'AHPr2'p5'AHPr2'p5'AHPr and p5'AOH2'p5'AOH2'p5'AOH, p5'A2'p5'A2'pAOH were slightly resistant to snake venom phosphodiesterase. The both circular dichroism and 1H-NMR spectra studies were used to characterize the modified 2'-5' oligoadenylates. Further, the biological activity evaluations of 8-substituted analogues of 2-5A are also described.
Kanou
M
M
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Ohomori
H
H
Takaku
H
H
Yokoyama
S
S
Kawai
G
G
Suhadolnik
R J
RJ
Sobol
R
R
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives*; D055598:Chemical Phenomena; D002621:Chemistry; D002942:Circular Dichroism; D004722:Endoribonucleases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009843:Oligoribonucleotides / Q000494:pharmacology; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D012335:RNA, Ribosomal / Q000378:metabolism; D014501:Uranium
D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; D012335:RNA, Ribosomal; D014501:Uranium; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom; D000241:Adenosine