Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*.
Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) alpha, delta, and epsilon*, with values for the Ki for PMPApp ((PMPApp)Ki) relative to the Km for dATP ((dATP)Km) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively.
Birkus
Gabriel
G
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic. Gabriel_Birkus@gilead.com
Hájek
Miroslav
M
Kramata
Pavel
P
Votruba
Ivan
I
Holý
Antonín
A
Otová
Berta
B
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors / Q000378:metabolism; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000068698:Tenofovir
D019380:Anti-HIV Agents; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase; D000225:Adenine