Inactivation of S-adenosyl-L-homocysteine hydrolase with novel 5′-thioadenosine derivatives.: Antiviral effects

被引：7
作者：
Guillerm, G
Guillerm, D
Vandenplas-Vitkowski, C
Glapski, C
De Clercq, E
机构：
[1] UFR Sci, Chim Bioorgan Lab, UMR 6519, F-51687 Reims 2, France
[2] Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 10期
关键词：
D O I：
10.1016/S0960-894X(03)00279-8
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Synthesis of 5'-S-vinyl-5'-thioadenosine 5, 5'-S-ethynyl-5'-thioadenosine 7 and 5'-S-cyano-5'-thioadenosine 9 is described. Incubation of AdoHcy hydrolase with 5, 7 and 9 resulted in time- and concentration-dependent inactivation of the enzyme and partial depletion of its NAD(+) content. From these results and characterisation of metabolites released during the inactivation process, hypothetical mechanisms are suggested. The antiviral activity of 5, 7 and 9 was examined. Significant activities were noted with 5 against Vaccinia, Junin and Taccaribe viruses. (C) 2003 Elsevier Science Ltd. All rights reserved.
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收藏
页码：1649 / 1652
页数：4
相关论文
共 23 条
  • [1] [Anonymous], 1996, ADV ANTIVIRAL DRUG D
  • [2] [Anonymous], BIOMEDICAL CHEM APPL
  • [3] CONVENIENT PREPARATION OF S-ADENOSYLHOMOCYSTEINE AND RELATED COMPOUNDS
    BORCHARDT, RT
    HUBER, JA
    WU, YS
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1976, 41 (03) : 565 - 567
  • [4] Synthesis, mechanism of action, and antiviral activity of a new series of covalent mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase
    Guillerm, G
    Guillerm, D
    Vandenplas-Witkowki, C
    Rogniaux, H
    Carte, N
    Leize, E
    Van Dorsselaer, A
    De Clercq, E
    Lambert, C
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (17) : 2743 - 2752
  • [5] INACTIVATION OF S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE BY CAMP RESULTS FROM DISSOCIATION OF ENZYME-BOUND NAD+
    HOHMAN, RJ
    GUITTON, MC
    VERON, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (14) : 4578 - 4581
  • [6] Crystal structure of S-adenosylhomocysteine hydrolase from rat liver
    Hu, YB
    Komoto, J
    Huang, Y
    Gomi, T
    Ogawa, H
    Takata, Y
    Fujioka, M
    Takusagawa, F
    [J]. BIOCHEMISTRY, 1999, 38 (26) : 8323 - 8333
  • [7] KITZ R, 1962, J BIOL CHEM, V237, P3245
  • [8] LEOPOLD WR, 1982, CANCER RES, V42, P4364
  • [9] VALIDATION OF THE GENERAL-PURPOSE QUANTA(R)3.2/CHARMM(R) FORCE-FIELD
    MOMANY, FA
    RONE, R
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 1992, 13 (07) : 888 - 900
  • [10] A SIMPLE, GENERAL PREPARATION OF S-ALKYL AND S-ARYL YNETHIOL ETHERS
    NEBOIS, P
    KANN, N
    GREENE, AE
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (23) : 7690 - 7692
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