Inhibition of deoxyribonucleic acid polymerases from human cells and from simian sarcoma virus by pyran.

Abstract

Pyrans are co-polymers of divinyl ether and maleic anhydride. Four pyrans of various molecular weights more potently inhibited terminal deoxyribonucleotidyltransferase (EC 2.7.7.31) from a human cell line of acute lymphoblastic leukemia origin (Molt-4) than they did DNA polymerases alpha, beta and gamma from these cells and DNA polymerase from simian sarcoma virus. For example, the concentrations of one pyran required for 50% inhibition of terminal deoxynucleotidyltransferase, DNA polymerases alpha, beta and gamma and viral DNA polymerase were 0.9, 110, 125, 35 and 47 microgram/ml respectively. Quantitatively similar results were obtained with the other pyrans. Inhibition of these enzymes by pyran was dependent on the concentrations of both the bivalent cation and template/primer or initiator in assay mixtures, but not on the concentrations of the substrate (deoxyribonucleoside 5'-triphosphate), enzyme, or bovine serum albumin. These results suggested that pyran inhibited these enzymes by complexing bivalent cations, which caused a decreased affinity of template/primer or initiator for each enzyme and a decrease in enzyme activity.

• Authors: R Dicioccio, B I Srivastava
• Journal: The Biochemical journal (Biochem J) Vol. 175 Issue 2 Pg. 519-24 (Nov 01 1978) ISSN: 0264-6021 [Print] England
• PMID: 217345 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nucleic Acid Synthesis Inhibitors
• Polymers
• Pyran Copolymer
• DNA Nucleotidylexotransferase

Topics

• Cell Line
• DNA Nucleotidylexotransferase (antagonists & inhibitors)
• Humans
• Kinetics
• Nucleic Acid Synthesis Inhibitors
• Polymers (pharmacology)
• Pyran Copolymer (pharmacology)
• Sarcoma Virus, Woolly Monkey (enzymology)