Synthesis and aminoacyl-tRNA synthetase inhibitory activity of aspartyl adenylate analogs

被引：41
作者：
Bernier, S
Akochy, PM
Lapointe, J
Chênevert, R
机构：
[1] Univ Laval, CREFSIP, Dept Chim, Fac Sci & Genie, Ste Foy, PQ G1K 7P4, Canada
[2] Univ Laval, Fac Sci & Genie, CREFSIP, Dept Biochim & Microbiol, Ste Foy, PQ G1K 7P4, Canada
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 01期
基金：
加拿大自然科学与工程研究理事会;
关键词：
aspartyl-tRNA synthetase; inhibitors; aspartyl adenylate; analogs;
D O I：
10.1016/j.bmc.2004.09.055
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：
Three nonhydrolyzable aspartyl adenylate analogs have been prepared and tested as inhibitors of E coli aspartyl-tRNA synthetase. 5'-O-[N-(L-Aspartyl)sulfamoyl]adenosine is a potent competitive inhibitor (K-i = 15 nM) whereas L-aspartol adenylate is a weaker inhibitor (K-i = 45 muM) with respect to aspartic acid. The corresponding ketomethylphosphonate (a novel isosteric replacement) is also a strong inhibitor (K-i = 123 nM). (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码：69 / 75
页数：7
相关论文
共 37 条
  • [1] Direct glutaminyl-tRNA biosynthesis and indirect asparaginyl-tRNA biosynthesis in Pseudomonas aeruginosa PAO1
    Akochy, PM
    Bernard, D
    Roy, PH
    Lapointe, J
    [J]. JOURNAL OF BACTERIOLOGY, 2004, 186 (03) : 767 - 776
  • [2] Patents on bacterial tRNA synthetase inhibitors: January 1996 to March 1999
    Beaulieu, D
    Ohemeng, KA
    [J]. EXPERT OPINION ON THERAPEUTIC PATENTS, 1999, 9 (08) : 1021 - 1028
  • [3] CRYSTAL-STRUCTURES AT 2.5 ANGSTROM RESOLUTION OF SERYL-TRANSFER-RNA SYNTHETASE COMPLEXED 2 ANALOGS OF SERYL ADENYLATE
    BELRHALI, H
    YAREMCHUK, A
    TUKALO, M
    LARSEN, K
    BERTHETCOLOMINAS, C
    LEBERMAN, R
    BEIJER, B
    SPROAT, B
    ALSNIELSEN, J
    GRUBEL, G
    LEGRAND, JF
    LEHMANN, M
    CUSACK, S
    [J]. SCIENCE, 1994, 263 (5152) : 1432 - 1436
  • [4] Synthesis of glutaminyl adenylate analogues that are inhibitors of glutaminyl-tRNA synthetase
    Bernier, S
    Dubois, DY
    Therrien, M
    Lapointe, J
    Chênevert, R
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (21) : 2441 - 2444
  • [5] The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate:: the mechanism of discrimination between asparagine and aspartic acid
    Berthet-Colominas, C
    Seignovert, L
    Härtlein, M
    Grotli, M
    Cusack, S
    Leberman, R
    [J]. EMBO JOURNAL, 1998, 17 (10) : 2947 - 2960
  • [6] tRNA discrimination at the binding step by a class II aminoacyl-tRNA synthetase
    Bovee, ML
    Yan, W
    Sproat, BS
    Francklyn, CS
    [J]. BIOCHEMISTRY, 1999, 38 (41) : 13725 - 13735
  • [7] Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases
    Brown, P
    Richardson, CM
    Mensah, LM
    O'Hanlon, PJ
    Osborne, NF
    Pope, AJ
    Walker, G
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1999, 7 (11) : 2473 - 2485
  • [8] SELECTIVE INHIBITION OF AMINOACYL RIBONUCLEIC ACID SYNTHETASES BY AMINOALKYL ADENYLATES
    CASSIO, D
    LEMOINE, F
    WALLER, JP
    SANDRIN, E
    BOISSONN.RA
    [J]. BIOCHEMISTRY, 1967, 6 (03) : 827 - &
  • [9] A FACILE SYNTHESIS OF ASCAMYCIN AND RELATED ANALOGS
    CASTROPICHEL, J
    GARCIALOPEZ, MT
    DELASHERAS, FG
    [J]. TETRAHEDRON, 1987, 43 (02) : 383 - 389
  • [10] THE ACTIVE-SITE OF YEAST ASPARTYL-TRANSFER-RNA SYNTHETASE - STRUCTURAL AND FUNCTIONAL-ASPECTS OF THE AMINOACYLATION REACTION
    CAVARELLI, J
    ERIANI, G
    REES, B
    RUFF, M
    BOEGLIN, M
    MITSCHLER, A
    MARTIN, F
    GANGLOFF, J
    THIERRY, JC
    MORAS, D
    [J]. EMBO JOURNAL, 1994, 13 (02) : 327 - 337
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