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).
Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague.
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I
Votruba
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Trávnícek
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Rosenberg
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M
Otmar
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Merta
H
H
Hrebabecký
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A
Holý
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