title: Carbocyclic dinucleoside polyphosphonates: interaction with HIV reverse transcriptase and antiviral activity.
abstract: 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.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anastasya L
authors.initials: AL
authors.lastname: Khandazhinskaya
authors.forename: Elena A
authors.initials: EA
authors.lastname: Shirokova
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Skoblov
authors.forename: Lyubov S
authors.initials: LS
authors.lastname: Victorova
authors.forename: Ludmila Ye
authors.initials: LY
authors.lastname: Goryunova
authors.forename: Robert S
authors.initials: RS
authors.lastname: Beabealashvilli
authors.forename: Tatyana R
authors.initials: TR
authors.lastname: Pronyaeva
authors.forename: Nina V
authors.initials: NV
authors.lastname: Fedyuk
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Zolin
authors.forename: Andrey G
authors.initials: AG
authors.lastname: Pokrovsky
authors.forename: Marina K
authors.initials: MK
authors.lastname: Kukhanova
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D003517:Cyclopentanes; D008081:Liposomes; D009705:Nucleosides; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; C020477:polyphosphonate; D054303:HIV Reverse Transcriptase