Effect of nucleic-acid-binding compounds on the hydrolytic activity of various ribonucleases.
Studies were conducted on the stimulatory effect that various nucleic-acid-binding compounds have on the hydrolysis of RNA and polyribonucleotides by pancreatic ribonuclease A and by other ribonucleases. The stimulatory activity of chloroquine on tRNA hydrolysis by pancreatic ribonuclease was due to the formation of oligonucleotides of a wide range of sizes and was not due to the formation of very short ( n greater than 5) oligonucleotide fragments of tRNA. The dextrorotatory and levorotatory isomers of chloroquine did not differ in their ability to stimulate the hydrolysis of tRNA by pancreatic ribonuclease A. In addition to chloroquine and primaquine, other nucleic-acid-binding compounds (e.g., quinacrine, lucanthone, and proflavin) stimulated the hydrolysis of tRNA by pancreatic ribonuclease A. Chloroquine did not alter the rate of hydrolysis by pancreatic ribonuclease A of low-molecular-weight substrates (cytidine cyclic 2':o'-monophosphate, uridine cyclic 2':3'-monophosphate, cytidylyl-adenosine, or uridylyl-uridine). Furthermore, chloroquine and primaquine did not affect the hydrolysis of poly(A) by high concentrations of pancreatic ribonuclease A. In studies on the hydrolysis of tRNA by other endoribonucleases, several of the nucleic-acid-binding compounds (e.g., quinacrine and ethidium) exhibited appreciable inhibition of both ribonuclease N1 and ribonuclease T1. None of the compounds tested stimulated the activity of ribonuclease T1, and only chloroquine, and perhaps lucanthone, stimulated the hydrolysis of tRNA by ribonuclease N1.
D000166:Acridines / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002738:Chloroquine / Q000494:pharmacology*; D004996:Ethidium / Q000494:pharmacology; D007700:Kinetics; D010179:Pancreas / Q000201:enzymology; D011319:Primaquine / Q000494:pharmacology*; D011370:Proflavine / Q000494:pharmacology*; D011485:Protein Binding; D011796:Quinacrine / Q000494:pharmacology*; D012260:Ribonucleases / Q000378:metabolism*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000166:Acridines; D000634:Aminoquinolines; D013096:Spermine; D002738:Chloroquine; D011370:Proflavine; D012260:Ribonucleases; D004996:Ethidium; D011796:Quinacrine; D011319:Primaquine; D013095:Spermidine