Evaluation and binding-mode prediction of thiopyrone-based inhibitors of anthrax lethal factor

被引：35

作者：

Lewis, Jana A.

Mongan, John

McCammon, J. Andrew

Cohen, Seth M.

机构：

[1] Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA 92093-0358

[2] Howard Hughes Medical Institute, Department of Pharmacology Bioinformatics Program, University of California, San Diego, San Diego, CA 92093-0365

来源：

CHEMMEDCHEM | 2006年 / 1卷 / 07期

关键词：

Computer chemistry; Drug design; Inhibitors; Metalloproteinases; Zinc;

D O I：

10.1002/cmdc.200600102

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Lethal weapon: Heterocyclic chelators have been identified for use in anthrax lethal factor inhibitors (LFi). A complete LFi (AM-2S, shown), which consists of a thiopyrone chelator and a simple biphenyl backbone, has an IC50 value in the low micromolar range. Potential binding modes for AM-2S were computationally examined, and the importance of a molecular surface solvent-solute boundary in such studies was demonstrated.

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页码：694 / +

页数：5

相关论文

共 26 条

[1] Anthrax lethal toxin: a weapon of multisystem destruction [J].

Agrawal, A ;

Pulendran, B .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2004, 61 (22) :2859-2865

[2] Electrostatics of nanosystems: Application to microtubules and the ribosome [J].

Baker, NA ;

Sept, D ;

Joseph, S ;

Holst, MJ ;

McCammon, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10037-10041

[3]

Case D, 2004, AMBER 9, V9

[4] Anthrax toxin [J].

Collier, RJ ;

Young, JAT .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2003, 19 :45-70

[5] A peptide-based fluorescence resonance energy transfer assay for Bacillus anthracis lethal factor protease [J].

Cummings, RT ;

Salowe, SP ;

Cunningham, BR ;

Wiltsie, J ;

Park, YW ;

Sonatore, LM ;

Wisniewski, D ;

Douglas, CM ;

Hermes, JD ;

Scolnick, EM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (10) :6603-6606

[6] Potent inhibitors of anthrax lethal factor from green tea [J].

Dell'Aica, I ;

Donà, M ;

Tonello, F ;

Piris, A ;

Mock, M ;

Montecucco, C ;

Garbisa, S .

EMBO REPORTS, 2004, 5 (04) :418-422

[7] Efficient synthetic inhibitors of anthrax lethal factor [J].

Forino, M ;

Johnson, S ;

Wong, TY ;

Rozanov, DV ;

Savinov, AY ;

Li, W ;

Fattorusso, R ;

Becattini, B ;

Orry, AJ ;

Jung, DW ;

Abagyan, RA ;

Smith, JW ;

Alibek, K ;

Liddington, RC ;

Strongin, AY ;

Pellecchia, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (27) :9499-9504

[8] Dual effect of synthetic aminoglycosides:: Antibacterial activity against Bacillus anthracis and inhibition of anthrax lethal factor [J].

Fridman, M ;

Belakhov, V ;

Lee, LV ;

Liang, FS ;

Wong, CH ;

Baasov, T .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (03) :447-452

[9] A new role for old ligands: Discerning chelators for zinc metalloproteinases [J].

Jacobsen, FE ;

Lewis, JA ;

Cohen, SM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (10) :3156-3157

[10] Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides [J].

Lee, LV ;

Bower, KE ;

Liang, FS ;

Shi, J ;

Wu, D ;

Sucheck, SJ ;

Vogt, PK ;

Wong, CH .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (15) :4774-4775