The effect of polyamines on the poly(adenylic acid)-induced inhibition of ribonuclease activity.
Segments of poly(A) at the 3'-termini of 5 S rRNA inhibit the activities of ribonucleases from Citrobacter, Enterobacter, bovine pancreas, human spleen and human plasma. Certain polyamines, or compounds containing polyamine substructures, mediate reversal of this inhibition. Effective compounds contain three amino groups, at least two of which are charged and are separated from the others by no less than three carbon atoms. Spermidine and 9-aminoacridines, which contain substituted propyl- or butylamino moieties at the 9-amino position and which bear two positive charges per molecule, are efficacious at low concentrations (5 microM). A decrease in effectiveness is associated with the removal of one aromatic ring from the 9-aminoacridines. However, the resulting 4-aminoquinolines, unlike the acridines, do not inhibit enzyme activity when present in concentrations above 30 microM. Relocating the diamino side chain from the 4- to the 8-position of the quinoline nucleus causes a decrease in charge density to +1, with the result that such compounds are ineffective. The orders of polyamine efficacy of reversal of inhibition were similar for enzymes from Citrobacter, bovine pancreas, and human plasma, and paralleled the order of binding of polyamines to either poly(A) or 5 S rRNA. This was not the case with Enterobacter and human spleen RNAases, indicating that the identity of the most effective polyamines depends on the RNAase studied. The combination of variable 3'-terminal poly(A) segment length and polyamine identity and concentration constitutes a system by which RNAase activities, and, therefore, substrate-degradation rates, may be easily varied.
D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002954:Citrobacter / Q000201:enzymology; D004754:Enterobacter / Q000201:enzymology; D006801:Humans; D046911:Macromolecular Substances; D010179:Pancreas / Q000201:enzymology; D011061:Poly A / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism; D012260:Ribonucleases / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000201:enzymology; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D011073:Polyamines; D012335:RNA, Ribosomal; D011061:Poly A; D012260:Ribonucleases