人类免疫缺陷病毒核壳体蛋白NCp7锌指受体抑制剂的研究进展

常昱;刘新泳

中国药学杂志 ›› 2007, Vol. 42 ›› Issue (01) : 9-12.

中国药学杂志 ›› 2007, Vol. 42 ›› Issue (01) : 9-12.
综述

人类免疫缺陷病毒核壳体蛋白NCp7锌指受体抑制剂的研究进展

  • 常昱;刘新泳
作者信息 +
文章历史 +

摘要

目的综述抗人类免疫缺陷病毒(H IV-1)药物新的作用靶点锌指受体的分子结构与功能以及针对于此靶点的抑制剂研究现状。方法以近几年国内外具有代表性的论文为基础,进行归纳整理。结果与结论H IV-1的锌指受体是病毒中高度保守的蛋白质结构,针对于此受体设计的药物可以有效阻止病毒的复制,且不易引起耐药性。

关键词

人类免疫缺陷病毒(HIV-1) / 锌指受体 / 核壳体蛋白7 / 研究进展

引用本文

导出引用
常昱;刘新泳. 人类免疫缺陷病毒核壳体蛋白NCp7锌指受体抑制剂的研究进展[J]. 中国药学杂志, 2007, 42(01): 9-12

参考文献

[1] TURPIN J A. The next generation of HIV/AIDS drugs: novel and developmental anti-HIV drugs and targets[J] . Expert Rev Anti Infect Ther,2003,1(1):97-128. [2] DRUILLENNEC S,ROQUES B P. HIV-1 NCp7 as a target for the design of novel antiviral agents[J] . Drug News Perspect,2000,13(6):337-349. [3] KANKIA B I,BARANY G,MUSIER-FORSYTH K. Unfolding of DNA quadruplexes induced by HIV-1 nucleocapsid protein[J] . Nucleic Acids Res,2005,33(14):4395-4403. [4] MORELLET N,DE ROCQUIGNY H,MELY Y,et al. Conformational behaviour of the active and inactive forms of the nucleocapsid NCp7 of HIV-1 studied by 1H-NMR[J] . J Mol Biol,1994,235:287-301. [5] MARK-DANIELI M,LAHAM N,KENAN-EICHLER M,et al. Single point mutations in the zinc finger motifs of the human immunodeficiency virus type 1 nucleocapsid alter RNA binding specificities of the gag protein and enhance packaging and infectivity[J] . J Virol,2005,9(12):7756-7767. [6] EGELE C,SCHAUB E,RAMALANJAONA N,et al. HIV-1 nucleocapsid protein binds to the viral DNA initiation sequences and chaperones their kissing interactions[J] . J Mol Biol,2004,342 (2) :453-466. [7] CAROLE B,SANDRINE J,DANIELA L. The chaperoning and assistance roles of the HIV-1 nucleocapsid protein in proviral DNA synthesis and maintenance[J] . Int J Biochem Cell Biol,2004,36:1668-1686. [8] BOMBARDA E,CHERRADI H,MORELLET N. Zn2+ Binding properties of single-point mutants of the C-terminal zinc finger of the HIV-1 nucleocapsid protein:evidence of a critical role of cysteine 49 in Zn2+dissociation[J] . Biochemistry,2002,41:4312-4320. [9] HONG M K,HARBRON E J,O'CONNOR D B,et al. Nucleic acid conformational hanges essential for HIV-1 nucleocapsid protein-mediated inhibition of self-priming in minus-strand transfer[J] . J Mol Biol,2003,325:1-10. [10] GOLINELLI M P,HUGHES S H. Self-priming of retroviral minus-strand strong-stop DNAs[J] . Virology,2001,285:278-290. [11] POLJAK L,BATSON S M,FICHEUX D,et al. Analysis of NCp7-dependent activation of HIV-1 cDNA integration and its conservation among retroviral nucleocapsid proteins[J] . J Mol Biol,2003,329: 411-421. [12] BUCKMAN J S,BOSCHE W J,GORELICK R J. Human immunodeficiency virus Type 1 nucleocapsid Zn2+ fingers are required for efficient reverse transcription,initial integration processes,and protection of newly synthesized viral DNA[J] . J Virol,2003,77: 1469-1480. [13] ERIK DE C. Novel compounds in preclinical/early clinical development for the treatment of HIV infections[J] . Rev Med Virol,2000,10:255-277. [14] ZHAO Q,EMST J T,HAMILTON A D,et al. XTT formazan widely used to detect cell viability inhibits HIV type 1 infection in vitro by targeting gp41[J] . AIDS Res Hum Retroviruses,2002,18(14):989-997. [15] HUANG M J,ANDREW M,JIM A,et al. Anti-HIV agents that selectively target retroviral nucleocapsid protein zinc fingers without affecting cellular zinc finger proteins[J] . J Med Chem,1998,41:1371-1381. [16] JENKINS L M,BYRD J C,HARA T,et al. Studies on the mechanism of inactivation of the HIV-1 nucleocapsid proteinNCp7 with 2-mercaptobenzamide thioesters[J] . J Med Chem,2005,48,2847-2858. [17] GOEBEL F D,HEMMER R,SCHMIT J C,et al. Phase I/II dose escalation and randomized withdrawal study with add-on azodicarbonamide in patients failing on current antiretroviral therapy[J] . AIDS,2001,15(1):33-45. [18] ERIK DE C. New developments in anti-HIV chemotherapy[J] . Farmaco,2001,(56):3-12. [19] VENKATESHA B,SONG Y S,SHARLYN J,et al. Inactivation of HIV-1 nucleocapsid protein P7 by pyridinioalkanoyl thioesters[J] . J Biol Chem,2000,275(20):14890-14897. [20] JIM A,TURPIN,SONG Y S,et al. Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers [J] . J Med Chem,1999 14;42(1):67-86. [21] SONG Y S,ATUL G,VENKATESHA B,et al. Synthesis and biological properties of amino acid amide ligand-based pyridinioalkanoyl thioesters as anti-HIV agents[J] . Bioorg Med Chem,2002,10(5):1263-1273. [22] WONDRAK E M,SAKAGUCHI K,RICE W G,et al. Removal of zinc Is required for processing of the mature nucleocapsid protein of human immunodeficiency virus,type 1,by the viral protease[J] . J Biol Chem,1994,269(35):21948-21950.

基金

国家自然基金资助项目(30371686);国际合作重点资助项目(2003DF000033);山东省自然基金资助项目(Y2003C11);山东省1020工程计划资助项目(卫2004-15)

Accesses

Citation

Detail

段落导航
相关文章

/