A new and potent 2-5A analogue which does not require a 5'-polyphosphate to activate mouse L-cell RNase L.
In order to explore the possibility of supplanting the requirement of a 5'-triphosphate moiety for the activation of the 2-5A-dependent endonuclease (RNase L) of mouse L-cells, two new tetrameric analogues of 2-5A were synthesized. The first tetramer, obtained by both a modified prebiotic synthetic approach as well as a phosphite triester solid phase oligonucleotide synthesis method, was p5'A2'p5'A2'p5'(br8A)2'p5'(br8A). The second oligonucleotide was derived from the former by a sequence involving periodate oxidation, reaction with n-hexylamine, and cyanoborohydride reduction, resulting in conversion of the 2'-terminal adenosine residue to 9-(3'-aza-4'-hexyl-1',2',3',4'-tetradeoxyhexopyranos-1(1)-yl)-8-++ +bromoadenine. Both of these oligomers, bearing only 5'-monophosphate groups, were found to be as potent as 2-5A itself as activators of the RNase L of mouse L-cells.
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Section on Biomedical Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Brozda
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D
Alster
D K
DK
Pabuccuoglu
A
A
Lesiak
K
K
D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012260:Ribonucleases / Q000378:metabolism*
D000227:Adenine Nucleotides; D003839:Deoxyadenosines; D009843:Oligoribonucleotides; D011500:Protein Synthesis Inhibitors; C076981:5'-monophosphoryladenylyl-(2'-5')adenylyl-(2'-5')-8-bromoadenylyl-(2'-5')-8-bromoadenosine; C076983:9-(3'-aza-4'-hexyl-1',2',3',4'-tetradeoxyhexopyranos-1'-yl)-8-bromoadenine; D012260:Ribonucleases