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.

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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 [J].

Akochy, PM ;

Bernard, D ;

Roy, PH ;

Lapointe, J .

JOURNAL OF BACTERIOLOGY, 2004, 186 (03) :767-776

[2] Patents on bacterial tRNA synthetase inhibitors: January 1996 to March 1999 [J].

Beaulieu, D ;

Ohemeng, KA .

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 [J].

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 .

SCIENCE, 1994, 263 (5152) :1432-1436

[4] Synthesis of glutaminyl adenylate analogues that are inhibitors of glutaminyl-tRNA synthetase [J].

Bernier, S ;

Dubois, DY ;

Therrien, M ;

Lapointe, J ;

Chênevert, R .

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 [J].

Berthet-Colominas, C ;

Seignovert, L ;

Härtlein, M ;

Grotli, M ;

Cusack, S ;

Leberman, R .

EMBO JOURNAL, 1998, 17 (10) :2947-2960

[6] tRNA discrimination at the binding step by a class II aminoacyl-tRNA synthetase [J].

Bovee, ML ;

Yan, W ;

Sproat, BS ;

Francklyn, CS .

BIOCHEMISTRY, 1999, 38 (41) :13725-13735

[7] Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases [J].

Brown, P ;

Richardson, CM ;

Mensah, LM ;

O'Hanlon, PJ ;

Osborne, NF ;

Pope, AJ ;

Walker, G .

BIOORGANIC & MEDICINAL CHEMISTRY, 1999, 7 (11) :2473-2485

[8] SELECTIVE INHIBITION OF AMINOACYL RIBONUCLEIC ACID SYNTHETASES BY AMINOALKYL ADENYLATES [J].

CASSIO, D ;

LEMOINE, F ;

WALLER, JP ;

SANDRIN, E ;

BOISSONN.RA .

BIOCHEMISTRY, 1967, 6 (03) :827-&

[9] A FACILE SYNTHESIS OF ASCAMYCIN AND RELATED ANALOGS [J].

CASTROPICHEL, J ;

GARCIALOPEZ, MT ;

DELASHERAS, FG .

TETRAHEDRON, 1987, 43 (02) :383-389

[10] THE ACTIVE-SITE OF YEAST ASPARTYL-TRANSFER-RNA SYNTHETASE - STRUCTURAL AND FUNCTIONAL-ASPECTS OF THE AMINOACYLATION REACTION [J].

CAVARELLI, J ;

ERIANI, G ;

REES, B ;

RUFF, M ;

BOEGLIN, M ;

MITSCHLER, A ;

MARTIN, F ;

GANGLOFF, J ;

THIERRY, JC ;

MORAS, D .

EMBO JOURNAL, 1994, 13 (02) :327-337

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