Biomaterial Database

Inhibition of hepatitis B Dane particle DNA polymerase activity by pyrophosphate analogs. 1980

E Nordenfelt, and B Oberg, and E Helgstrand, and E Miller

A DNA polymerase is associated with the core of the so-called Dane particles. The probability that this is the hepatitis B viral DNA polymerase offers the possibility of preventing hepatitis B multiplication by selective inhibition of this enzyme. We have previously reported that trisodium phosphonoformate (PFA) inhibits Dane particle DNA polymerase. Fifteen compounds with structural similarity to PFA and pyrophosphate have now been tested for inhibition of hepatitis B virus DNA polymerase in an attempt to define the structural requirement for the inhibition. Active structures have two acid groups at close proximity of which at least one is a phosphono group. Phosphonoformate and hypophosphare were the two most active inhibitors. The Ki value for PFA was 7.2 microM when dTTP was used as variable substrate, and the mechanism of inhibition was non-competitive. Phosphonoformate caused rapid shut-off of the polymerase reaction, indicating that it might inhibit elongation. The efficient inhibition of hepatitis B virus DNA polymerase by PFA and its low toxicity suggest that it could be used to inhibit hepatitis B virus multiplication in vivo.

UI	MeSH Term	Description	Entries
D011756	Diphosphates	Inorganic salts of phosphoric acid that contain two phosphate groups.	Diphosphate,Pyrophosphate Analog,Pyrophosphates,Pyrophosphate Analogs,Analog, Pyrophosphate
D006515	Hepatitis B virus	The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum.	Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D019384	Nucleic Acid Synthesis Inhibitors	Compounds that inhibit cell production of DNA or RNA.	DNA Polymerase Inhibitor,DNA Synthesis Inhibitor,DNA Synthesis Inhibitors,Nucleic Acid Synthesis Inhibitor,RNA Synthesis Inhibitor,RNA Synthesis Inhibitors,DNA Polymerase Inhibitors,Inhibitors, DNA Synthesis,Inhibitors, Nucleic Acid Synthesis,Inhibitors, RNA Synthesis,Inhibitor, DNA Polymerase,Inhibitor, DNA Synthesis,Inhibitor, RNA Synthesis,Inhibitors, DNA Polymerase,Polymerase Inhibitor, DNA,Polymerase Inhibitors, DNA,Synthesis Inhibitor, DNA,Synthesis Inhibitor, RNA,Synthesis Inhibitors, DNA,Synthesis Inhibitors, RNA