Bidirectional effectors of a group I intron ribozyme from Pneumocystis carinii.
The L-arginine acts stereoselectively on the Pc1.LSU nuclear group I intron of Pneumocystis carinii, competitively inhibiting the first step of the splicing reaction and stimulating the second step. A number of arginine-related compounds are more potent than L-arginine as stimulators and inhibitors. The most potent peptides tested are 10,000 times as effective as L-arginine in inhibiting ribozyme activity, and nearly 400 times as effective as stimulators. This phenomenon indicates that ribozymes, like protein enzymes, can interact with non-substrate low molecular weight compounds, and that non-nucleic acid agents might be developed as drugs acting on RNA targets.
Liu
Y
Y
Department of Molecular Genetics and Microbiology, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.
Leibowitz
M J
MJ
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D007438:Introns; D009894:Opportunistic Infections / Q000188:drug therapy; D011010:Pneumocystis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy; D012326:RNA Splicing / Q000187:drug effects; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D000935:Antifungal Agents; D016337:RNA, Catalytic