Inhibition of avian myeloblastosis virus reverse transcriptase by diphosphates of acyclic phosphonylmethyl nucleotide analogues.
Diphosphates of N-(2-phosphonylmethoxyethyl) derivatives of heterocyclic bases were studied in the endogenous oligo(dT)12-18 primed reaction of reverse transcriptase from detergent-disrupted AMV(MAV) retrovirions. These diphosphates (analogues of nucleotide 5'-triphosphates) exhibited an inhibitory activity towards reverse transcriptase. This inhibitory activity was dependent on the character of the heterocyclic base and decreased in the order: 2-aminoadenine greater than adenine greater than guanine much greater than cytosine much greater than thymine greater than uracil. The 2-aminoadenine derivative was more potent than either AZT-TP or ddTTP, while PMEApp had approximately the same potency as the two reference compounds (IC50 approximately 1 microM at 20 microM competing substrate). This finding is consistent with the antiviral activity of the parent nucleotide analogues against retroviruses (including HIV).
Votruba
I
I
Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague.
Trávnícek
M
M
Rosenberg
I
I
Otmar
M
M
Merta
A
A
Hrebabecký
H
H
Holý
A
A
D000225:Adenine / Q000031:analogs & derivatives; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D009189:Avian Myeloblastosis Virus / Q000187:drug effects / Q000201:enzymology*; D002645:Chickens; D003596:Cytosine / Q000031:analogs & derivatives; D006147:Guanine / Q000031:analogs & derivatives; D009711:Nucleotides / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D013936:Thymidine / Q000031:analogs & derivatives; D014498:Uracil / Q000031:analogs & derivatives
D000998:Antiviral Agents; D009711:Nucleotides; D010710:Phosphates; D018894:Reverse Transcriptase Inhibitors; D014498:Uracil; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013936:Thymidine