HIV-1逆转录酶的二聚化及其抑制剂的研究进展

王岩;刘新泳

中国药学杂志 ›› 2009, Vol. 44 ›› Issue (04) : 241-244.

中国药学杂志 ›› 2009, Vol. 44 ›› Issue (04) : 241-244.
综述

HIV-1逆转录酶的二聚化及其抑制剂的研究进展

  • 王岩;刘新泳
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摘要

目的综述HIV-1逆转录酶的二聚化及其抑制剂的研究进展。方法查阅近年相关文献,进行分析评述。结果与结论酶的二聚化是逆转录酶发挥功能所必需的,抑制逆转录酶二聚化成为近年来研究抗HIV药物的一个新的靶点,现已发现的两类二聚化抑制剂为研究新的抗HIV药物提供了基础。

关键词

HIV-1 / 逆转录酶 / 二聚化 / 抑制剂

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导出引用
王岩;刘新泳. HIV-1逆转录酶的二聚化及其抑制剂的研究进展[J]. 中国药学杂志, 2009, 44(04): 241-244

参考文献

[1] DEL RIO C. Current concepts in antiretroviral therapy failure [J]. Top HIV Med,2006,14(3):102-106. [2] SRIVASTAVA S,SLUIS-CREMER N,TACHEJIAN G. Dimerization of human immunodeficiency virus type 1 reverse transcriptase as an antiviral target [J]. Curr Pharm Des,2006,12(15):1879-1894. [3] BALZARINI J,AUWERX J,RODRIGUEZ-BARRIOS F,et al. The amino acid N136 in HIV-1 reverse transcriptase (RT) maintains efficient association of both Rtsubunits and enables the rational design of novel RT inhibitors [J]. Mol Pharmacol,2005,68(1): 49-60. [4] AUWERX J,YAN-NIEUWENHOVE J,RODRIGUEZ-BARRIOS F,et al. The N137 and P140 amino acids in the p51 and the P95 amino acid in the p66 subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are instrumental to maintain catalytic activity and to design new classes of anti-HIV-1 drugs [J]. FEBS Letters,2005,579(11): 2294-2300. [5] JANSSEN P A,LEWI P J,ARNOLD E,et al. In search of a novel anti-HIV drug:multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (R278474,Rilpivirine) [J]. J Med Chem,2005,48(6):1901-1909. [6] BELOV D A,VESELOVSKII A V. Analysis of contact interfaces of HIV reverse transcriptase subunits [J]. Biomed Khim,2006,52(1):19-28. [7] ALOK MULKY,CHRISTIE VU B,CONWAY JOAN A,et al. Analysis of amino acids in the β7-β8 loop of human immunodeficiency virus type 1 reverse transcriptase for their role in Virus Replication[J]. J Mol Biol,2007,365(5): 1368-1378. [8] LEVY Y,CAFLISCH A,ONUCHIC J N,et al. The folding and dimerization of HIV-1 protease:Evidence for a stable monomer from simulations [J]. J Mol Biol,2004,340(1):67-79. [9] SLUIS-CREMER N,ARION D,ABRAM M E,et al. Proteolytic processing of an HIV-1 pol polyprotein precursor:insights into the mechanism of reverse transcriptase p66/p51 heterodimer formation [J]. Int J Biochem Cell Biol,2004,36(9):1836–1847. [10] DE SOULTRAIT V R,DESJOBERT C,TARRAGO-LITVAK L.Peptides as new inhibitors of HIV-1 reverse transcriptase and integrase [J].Curr Med Chem,2003,10(18):1765-1778. [11] DIVITA G,RESTLE T,GOODY R.S,et al. Inhibition of human immunodeficiency virus type 1 reverse transcriptase dimerization using synthetic peptides derived from the connection domain[J]. J Biol Chem,1994,269(18):13080-13083. [12] MORRIS M C,ROBERT-HEBMANN V,CHALOIN L,et al. A new potent HIV-1 reverse transcriptase inhibitor. A synthetic peptide derived from the interface subunit domains[J]. J Biol Chem,1999,274(35): 24941-24946. [13] DEPOLLIER J,HOURDOU M L,ALDRIAN-HERRADA G,et al. Insight into the mechanism of a peptide inhibitor of HIV reverse transcriptase dimerization [J]. Biochemistry,2005,44(6): 1909-1918. [14] MORRIS M C,BERDUCOU C,MERY J,et al. The thumb domain of the P51-subunit is essential for activation of HIV reverse transcriptase [J].Biochemistry,1999,38(46): 15097-150103. [15] CAMARASA M J,VELAZQUEZ S,SAN-FELIX A,et al. TSAO derivatives,inhibitors of HIV-1 reverse transcriptase dimerization: recent progress [J]. Curr Pharm Des,2006,12(15): 1895-1907. [16] CAMARASA M J,VELAZQUEZ S,SAN-FELIX A,et al. TSAO derivatives the first non-peptide inhibitors of HIV-1 RT dimerization [J]. Antivir Chem Chemother,2005,16(3): 147-153. [17] RODRIGUEZ-BARRIOS F,PEREZ C,LOBATON E,et al. Identification of a putative binding site for [2',5'-bis- O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)thymine (TSAO) derivatives at the p51-p66 interface of HIV-1 reverse transcriptase [J]. J Med Chem,2001,44(12):1853-1865. [18] CAMARASA M J,VELAZQUEZ S,SAN-FELIX A,et al. Dimerization inhibitors of HIV-1 reverse transcriptase,protease and integrase:A single mode of inhibition for the three HIV enzymes[J]. Antiviral Research,2006,71(2-3):260-267. [19] AUWERX J,RODRIGUEZ-BARRIOS F,CECCHERINI- SILBERSTEIN F,et al. Role of T139 in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitivity to (+)-calanolide A [J]. Mol Pharmacol,2005,68(3): 652-659. [20] SLUIS-CREMER N,HAMAMOUCH N,SAN FELIX A,et al. Structure-activity relationships of [2',5'-bis-O-(tert-butyldimethyl- silyl)-beta-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1',2''-oxathiole- 2'',2''-dioxide)thymine derivatives as inhibitors of HIV-1 reverse transcriptase dimerization [J]. J Med Chem,2006,49(16): 4834-4841. [21] BONACHE M C,CHAMORRO C,VELAZQUEZ S,et al. Improving the antiviral efficacy and selectivity of HIV-1 reverse transcriptase inhibitor TSAO-T by the introduction of functional groups at the N-3 position [J]. J Med Chem,2005,48(21): 6653-6660. [22] SLUIS-CREMER N,ARION D,MICHAEL A P. Destabilization of the HIV-1 reverse transcriptase dimer upon interaction with N-acyl hydrazone inhibitors [J]. Mol Pharmacol,2002,62(2):398-405.

基金

国家自然基金资助项目(30772629;30371686);国际合作重点项目(2003DF000033)

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