Abstract
β-Alanyltyrosine derivative of 2', 5'-tetraadenylate 5'-triphosphate, pppA2'p5'A2'-p5'A2'p5'A-β-Ala-Tyr was prepared by coupling of periodate-oxidized pppA2'p5'-A2'p5'A2'p5'A with β-alanyltyrosine methyl ester, followed by reduction with sodium cyanoborohydride. Its stability to 2', 5'-phosphodiesterase and phosphatase was investigated in mouse L cell extract. The 5'-triphosphate of the compound was cleaved gradually to form the 5'-dephosphorylated derivative, A2'p5'A2'p5'A2'p5'A-β-Ala-Tyr, followed by slow degradation of the 2', 5'-phosphodiester bond. On the other hand, pppA2'p5'A2'p5'A2'p5'A was hydrolyzed very quickly under the same conditions. The tetramer derivative bound tightly to the 2', 5'-oligoadenylatedependent endoribonuclease in rabbit reticulocyte lysate or mouse L cell extract and inhibited protein synthesis of mouse L cells more effectively than the unmodified 2', 5'-tetraadenylate 5'-triphosphate. The corresponding trimer derivative had slightly weaker activities than the unmodified trimer for binding to the endoribonuclease and for inhibition of protein synthesis. The compound, pppA2'p5'A2'p5'-A2'p5'A-β-Ala-Tyr, was iodinated easily at the tyrosine residue with125I, giving a high-specific-radioactivity derivative which was used as a radio-labeled probe in a radiobinding assay for 2', 5'-oligoadenylate.
