Carbocyclic dinucleoside polyphosphonates: interaction with HIV reverse transcriptase and antiviral activity.
Carbocyclic alpha, gamma-bis(nucleoside)-5,5'-triphosphonates and alpha, delta-bis(nucleoside)-5,5'-tetraphosphonates (Ap4A and Gp4G) analogues were shown to be a new type of terminating substrate of HIV reverse transcriptase. They effectively inhibited the DNA synthesis catalyzed by this enzyme in model cell-free systems, but their antiviral activity both in Rat1 fibroblast cell culture bearing MLV reverse transcriptase and in HIV-infected MT-4 cells was low. When a liposome delivery system was used, the antiviral efficacy of the compounds under study was increased.
Khandazhinskaya
Anastasya L
AL
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Shirokova
Elena A
EA
Skoblov
Yurii S
YS
Victorova
Lyubov S
LS
Goryunova
Ludmila Ye
LY
Beabealashvilli
Robert S
RS
Pronyaeva
Tatyana R
TR
Fedyuk
Nina V
NV
Zolin
Vladimir V
VV
Pokrovsky
Andrey G
AG
Kukhanova
Marina K
MK
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D008081:Liposomes; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D003517:Cyclopentanes; D008081:Liposomes; D009705:Nucleosides; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; C020477:polyphosphonate; D054303:HIV Reverse Transcriptase