34051-12-2Relevant academic research and scientific papers
Synthesis, Characterization, and Biological Properties of 8-Azido- and 8-Amino-Substituted 2′,5′-Oligoadenylates
Sawai, Hiroaki,Hirano, Atushi,Mori, Hiroyuki,Shinozuka, Kazuo,Dong, Beihua,Silverman, Robert H.
, p. 4926 - 4932 (2003)
A series of 8-azido- and 8-amino-substituted 2′,5′ -oligoadenylatyes was prepared by a uranylion catalyzed polymerization of the corresponding 8-substituted adenosine phosphorimidazolide. Subsequent 5′-dephosphorylation of the resulting 5′-phosphoryl 2′,5′-linked oligomers with alkaline phosphatase gave the corresponding core oligomers. The CD spectra indicated that the 8-aminoadenosine analogue of the 2′,5′-linked trimer has an anti-orientation as in naturally occurring 2′,5′-oligoadenylates, while 8-azido-substituted 2′,5′-oligoadenylates have a synorientation. The 8-substituted oligomers showed enhanced resistance against digestion by snake venom phosphodiesterase. The 2′,5′-linked 8-azidoadenylate trimer and tetramer displayed strong RNase L binding and activating ability, although the corresponding dimer is devoid of such activities. In contrast, very low or no RNase L binding and activating ability were observed in the 8-aminoadenosine analogue of 2′,5′ -oligoadenylates. Results indicate that the bulkiness and ionic character of the 8-substituting group have significant effects on the ability of these analogues to bind and activate RNase L. Furthermore, the orientation of the glycosidic base in the 2-5A analogues may change from syn to anti during binding to RNase L. The 8-azido-adenosine analogues of 2-5A will be useful tools in the photoaffinity labeling of RNase L, due to their strong RNase L binding ability. In addition, these 8-azidoadenosine compounds may be considered as candidates for experimental therapeutic agents because they have enhanced stability to enzyme degradation while retaining the ability to activate RNase L.
