Oligonucleotide structural features involved in binding to and activation of the 2-5A-dependent endoribonuclease of L cells.
Several analogues of 2-5A were prepared and evaluated for their ability to bind to and/or activate the 2-5A dependent endonuclease from murine L cells. Replacement of one of the two 2',5'-phosphodiester bonds of ppp5'A2'p5'A2'p5'A with 3',5'-phosphodiester bonds gave analogues 40-50 X less active than 2-5A in binding to or activation of the 2-5A-activated endonuclease whereas replacement of both 2',5'-linkages with 3',5'-linkage resulted in a compound (3-5A) which was 10,000 X less effective in binding to the endonuclease and devoid of activity as an inhibitor of protein synthesis. The sequence of periodate oxidation/Schiff base formation/borohydride reduction gave a derivative of ppp5'A2'p5'A2'p5'A2'p5'A in which the 2'-terminal ribose was replaced with a N-hexyl morpholine ring. This material was 10 X more active than 2-5A an a inhibitor of translation. One possible explanation for this increased activity is that the 2'-terminally modified oligomer is resistant to degradation by the 2',5'-phosphodiesterase responsible for the degradation of 2-5A in cell extracts.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D004722:Endoribonucleases / Q000378:metabolism*; D004789:Enzyme Activation; D007700:Kinetics; D007739:L Cells / Q000201:enzymology; D051379:Mice; D009841:Oligonucleotides / Q000378:metabolism*; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000227:Adenine Nucleotides; D009841:Oligonucleotides; D009843:Oligoribonucleotides; C023505:2',5'-oligoadenylate; C033547:2'-5'-oligo(A)-dependent endonuclease; D004722:Endoribonucleases