Hydrophobic benzoic acids as inhibitors of influenza neuraminidase

被引：38
作者：
Atigadda, VR
Brouillette, WJ [1 ]
Duarte, F
Babu, YS
Bantia, S
Chand, P
Chu, NM
Montgomery, JA
Walsh, DA
Sudbeck, E
Finley, J
Air, GM
Luo, M
Laver, GW
机构：
[1] Univ Alabama, Dept Chem, Birmingham, AL 35294 USA
[2] Univ Alabama, Ctr Macromol Crystallog, Birmingham, AL 35294 USA
[3] BioCryst Pharmaceut Inc, Birmingham, AL 35244 USA
[4] Univ Oklahoma, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA
[5] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 11期
关键词：
neuraminidase; influenza virus; sialidase; structure-based drug design;
D O I：
10.1016/S0968-0896(99)00197-2
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts In a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC50 1 mu M) over type B (B/Lee/40) influenza NA (IC50 500 mu M). (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：2487 / 2497
页数：11
相关论文
共 32 条
  • [1] THE NEURAMINIDASE OF INFLUENZA-VIRUS
    AIR, GM
    LAVER, WG
    [J]. PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1989, 6 (04): : 341 - 356
  • [2] BABU YS, Patent No. 9747194
  • [3] 3-DIMENSIONAL STRUCTURE OF NEURAMINIDASE OF SUBTYPE-N9 FROM AN AVIAN INFLUENZA-VIRUS
    BAKER, AT
    VARGHESE, JN
    LAVER, WG
    AIR, GM
    COLMAN, PM
    [J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 1987, 2 (02) : 111 - 117
  • [4] 3-DIMENSIONAL STRUCTURE OF INFLUENZA-A N9 NEURAMINIDASE AND ITS COMPLEX WITH THE INHIBITOR 2-DEOXY 2,3-DEHYDRO-N-ACETYL NEURAMINIC ACID
    BOSSARTWHITAKER, P
    CARSON, M
    BABU, YS
    SMITH, CD
    LAVER, WG
    AIR, GM
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1993, 232 (04) : 1069 - 1083
  • [5] THE 2.2-A RESOLUTION CRYSTAL-STRUCTURE OF INFLUENZA-B NEURAMINIDASE AND ITS COMPLEX WITH SIALIC-ACID
    BURMEISTER, WP
    RUIGROK, RWH
    CUSACK, S
    [J]. EMBO JOURNAL, 1992, 11 (01) : 49 - 56
  • [6] Site-directed mutagenesis of catalytic residues of influenza virus neuraminidase as an aid to drug design
    Ghate, AA
    Air, GM
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1998, 258 (02): : 320 - 331
  • [7] INHIBITION OF SIALIDASES FROM VIRAL, BACTERIAL AND MAMMALIAN SOURCES BY ANALOGS OF 2-DEOXY-2,3-DIDEHYDRO-N-ACETYLNEURAMINIC ACID MODIFIED AT THE C-4 POSITION
    HOLZER, CT
    VONITZSTEIN, M
    JIN, B
    PEGG, MS
    STEWART, WP
    WU, WY
    [J]. GLYCOCONJUGATE JOURNAL, 1993, 10 (01) : 40 - 44
  • [8] STRUCTURE OF INFLUENZA-VIRUS NEURAMINIDASE B/LEE/40 COMPLEXED WITH SIALIC-ACID AND A DEHYDRO ANALOG AT 1.8-ANGSTROM RESOLUTION - IMPLICATIONS FOR THE CATALYTIC MECHANISM
    JANAKIRAMAN, MN
    WHITE, CL
    LAVER, WG
    AIR, GM
    LUO, M
    [J]. BIOCHEMISTRY, 1994, 33 (27) : 8172 - 8179
  • [9] STRUCTURES OF AROMATIC INHIBITORS OF INFLUENZA-VIRUS NEURAMINIDASE
    JEDRZEJAS, MJ
    SINGH, S
    BROUILLETTE, WJ
    LAVER, WG
    AIR, GM
    LUO, M
    [J]. BIOCHEMISTRY, 1995, 34 (10) : 3144 - 3151
  • [10] GS4071 is a slow-binding inhibitor of influenza neuraminidase from both A and B strains
    Kati, WM
    Saldivar, AS
    Mohamadi, F
    Sham, HL
    Laver, WG
    Kohlbrenner, WE
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 244 (02) : 408 - 413
1234