Carbocyclic dinucleoside polyphosphonates: Interaction with HIV reverse transcriptase and antiviral activity

被引：28

作者：

Khandazhinskaya, AL

Shirokova, EA

Skoblov, YS

Victorova, LS

Goryunova, LY

Beabealashvilli, RS

Pronyaeva, TR

Fedyuk, NV

Zolin, VV

Pokrovsky, AG

Kukhanova, MK

机构：

[1] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia

[2] Univ Oslo, Moscow Ctr Med Studies, Moscow, Russia

[3] SRC Virol & Biotechnol Vector, Koltsov 630059, Russia

[4] Natl Cardiol Res Ctr, Inst Expt Cardiol, Moscow, Russia

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 06期

关键词：

D O I：

10.1021/jm011011l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

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页码：1284 / 1291

页数：8

相关论文

共 27 条

[1] DISMUTATION REACTIONS OF NUCLEOSIDE POLYPHOSPHATES .V. SYNTHESES OF P1 P4-DI(GUANOSINE-5') TETRAPHOSPHATE AND P1 P3-DI(GUANOSINE-5') TRIPHOSPHATE [J].

ADAM, A ;

MOFFATT, JG .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1966, 88 (04) :838-&

[2] gamma-phosphate-substituted 2'-deoxynucleoside 5'-triphosphates as substrates for DNA polymerases [J].

Arzumanov, AA ;

Semizarov, DG ;

Victorova, LS ;

Dyatkina, NB ;

Krayevsky, AA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) :24389-24394

[3] New antivirals - mechanism of action and resistance development [J].

Balzarini, J ;

Naesens, L ;

De Clercq, E .

CURRENT OPINION IN MICROBIOLOGY, 1998, 1 (05) :535-546

[4]

CHENG YC, 1987, J BIOL CHEM, V262, P2187

[5] ANTIVIRAL EFFICACY, INTRACELLULAR UPTAKE AND PHARMACOKINETICS OF FREE AND LIPOSOME-ENCAPSULATED 2',3'-DIDEOXYINOSINE [J].

DESORMEAUX, A ;

HARVIE, P ;

PERRON, S ;

MAKABIPANZU, B ;

BEAUCHAMP, D ;

TREMBLAY, M ;

POULIN, L ;

BERGERON, MG .

AIDS, 1994, 8 (11) :1545-1553

[6] SYNTHESIS OF 4 STEREOISOMERS OF CARBOCYCLIC 5'-NOR D4A AND EVALUATION OF THEIR TRIPHOSPHATES AS SUBSTRATES FOR DNA-POLYMERASES [J].

DYATKINA, N ;

SEMIZAROV, D ;

VICTOROVA, L ;

KRAYEVSKY, A ;

THEIL, F ;

VONJANTALIPINSKI, M .

NUCLEOSIDES & NUCLEOTIDES, 1995, 14 (3-5) :723-726

[7] PHOSPHORYLATION OF 3'-AZIDO-3'-DEOXYTHYMIDINE AND SELECTIVE INTERACTION OF THE 5'-TRIPHOSPHATE WITH HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE [J].

FURMAN, PA ;

FYFE, JA ;

STCLAIR, MH ;

WEINHOLD, K ;

RIDEOUT, JL ;

FREEMAN, GA ;

LEHRMAN, SN ;

BOLOGNESI, DP ;

BRODER, S ;

MITSUYA, H ;

BARRY, DW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (21) :8333-8337

[8] CARBODIIMIDES .5. A NOVEL SYNTHESIS OF ADENOSINE DIPHOSPHATE AND TRIPHOSPHATE AND P1,P2-DIADENOSINE-5'-PYROPHOSPHATE [J].

KHORANA, HG .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1954, 76 (13) :3517-3522

[9]

KRAEV A S, 1988, Molekulyarnaya Biologiya (Moscow), V22, P1164

[10] THE INTERACTION OF THE RECOGNITION HELIX OF LAC REPRESSOR WITH LAC OPERATOR [J].

LEHMING, N ;

SARTORIUS, J ;

NIEMOLLER, M ;

GENENGER, G ;

VONWILEKENBERGMANN, B ;

MULLERHILL, B .

EMBO JOURNAL, 1987, 6 (10) :3145-3153