Systematic investigation of non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs)

被引:6
作者
Beyer, A
Lawtrakul, L
Hannongbua, S
Wolschann, P
机构
[1] Res Inst Mol Pathol, A-1030 Vienna, Austria
[2] Thammasat Univ, SIIT, Dept Common & Grad Studies, Pathum Thani 12121, Thailand
[3] Kasetsart Univ, Fac Sci, Dept Chem, Bangkok 10900, Thailand
[4] Inst Theoret Chem & Struct Biol, A-1090 Vienna, Austria
来源
MONATSHEFTE FUR CHEMIE | 2004年 / 135卷 / 08期
关键词
non-nucleoside reverse transcriptase inhibitors (NNRTIs); inhibition mechanism; viral mutation; drug resistance;
D O I
10.1007/s00706-004-0173-y
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The 44 crystal structures of NNRTIs complexed with HIV-1 reverse transcriptase (RT) have been analyzed in detail especially the orientation geometries and the distances between inhibitor molecules and surrounding amino acids. In general, various NNIs bind to the same region of the HIV-1 RT in the palm subdomain of p66, but subtle differences in individual interactions between RT and its inhibitors can be detected by comparison of all structures in this study.
引用
收藏
页码:1047 / 1059
页数:13
相关论文
共 34 条
  • [1] 2',5'-BIS-O-(TERT-BUTYLDIMETHYLSILYL)-3'-SPIRO-5''-(4''-AMINO-1',2''-OXATHIOLE-2'',2''-DIOXIDE)PYRIMIDINE (TSAO) NUCLEOSIDE ANALOGS - HIGHLY SELECTIVE INHIBITORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 THAT ARE TARGETED AT THE VIRAL REVERSE-TRANSCRIPTASE
    BALZARINI, J
    PEREZPEREZ, MJ
    SANFELIX, A
    SCHOLS, D
    PERNO, CF
    VANDAMME, AM
    CAMARASA, MJ
    DECLERCQ, E
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) : 4392 - 4396
  • [2] Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant
    Das, K
    Ding, JP
    Hsiou, Y
    Clark, AD
    Moereels, H
    Koymans, L
    Andries, K
    Pauwels, R
    Janssen, PAJ
    Boyer, PL
    Clark, P
    Smith, RH
    Smith, MBK
    Michejda, CJ
    Hughes, SH
    Arnold, E
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1996, 264 (05) : 1085 - 1100
  • [3] Perspectives of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection
    De Clercq, E
    [J]. FARMACO, 1999, 54 (1-2): : 26 - 45
  • [4] The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection
    De Clercq, E
    [J]. ANTIVIRAL RESEARCH, 1998, 38 (03) : 153 - 179
  • [5] AN ANTIVIRAL TARGET ON REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVEALED BY TETRAHYDROIMIDAZO[4,5,1-JK][1,4]BENZODIAZEPIN-2(1H)-ONE AND TETRAHYDROIMIDAZO-[4,5,1-JK][1,4]BENZODIAZEPIN-2(1H)-ONE-THIONE DERIVATIVES
    DEBYSER, Z
    PAUWELS, R
    ANDRIES, K
    DESMYTER, J
    KUKLA, M
    JANSSEN, PAJ
    DECLERCQ, E
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (04) : 1451 - 1455
  • [6] *DEP BIOCH MOL BIO, 1998, TINKER SOFTW TOOLS M
  • [7] STRUCTURE OF HIV-1 RT/TIBO R-86183 COMPLEX REVEALS SIMILARITY IN THE BINDING OF DIVERSE NONNUCLEOSIDE INHIBITORS
    DING, JP
    DAS, K
    MOEREELS, H
    KOYMANS, L
    ANDRIES, K
    JANSSEN, PAJ
    HUGHES, SH
    ARNOLD, E
    [J]. NATURE STRUCTURAL BIOLOGY, 1995, 2 (05): : 407 - 415
  • [8] MECHANISM OF INHIBITION OF HIV-1 REVERSE-TRANSCRIPTASE BY NONNUCLEOSIDE INHIBITORS
    ESNOUF, R
    REN, JS
    ROSS, C
    JONES, Y
    STAMMERS, D
    STUART, D
    [J]. NATURE STRUCTURAL BIOLOGY, 1995, 2 (04): : 303 - 308
  • [9] FRISCH MJ, 1995, GAUSSIAN 94 VERS B 3
  • [10] PYRIDINONE DERIVATIVES - SPECIFIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE INHIBITORS WITH ANTIVIRAL ACTIVITY
    GOLDMAN, ME
    NUNBERG, JH
    OBRIEN, JA
    QUINTERO, JC
    SCHLEIF, WA
    FREUND, KF
    GAUL, SL
    SAARI, WS
    WAI, JS
    HOFFMAN, JM
    ANDERSON, PS
    HUPE, DJ
    EMINI, EA
    STERN, AM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (15) : 6863 - 6867