Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A

被引：42

作者：

Chenna, Bala Chandra ^{[1
]}

Shinkre, Bidhan A. ^{[1
]}

King, Jason R. ^{[1
]}

Lucius, Aaron L. ^{[1
]}

Narayana, Sthanam V. L. ^{[2
]}

Velu, Sadanandan E. ^{[1
]}

机构：

[1] Univ Alabama, Dept Chem, Birmingham, AL 35294 USA

[2] Univ Alabama, Sch Optometry, Ctr Biophys Sci & Engn, Birmingham, AL 35294 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 01期

关键词：

D O I：

10.1016/j.bmcl.2007.10.051

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

In-silico virtual screening of bacterial surface enzyme Staphylococcus aureus Sortase A against commercial compound libraries using FlexX software package has led to the identification of novel inhibitors. Inhibition of enzyme catalytic activity was deter-mined by monitoring the steady state cleavage of a model peptide substrate. Preliminary structure activity relationship studies on the lead compound resulted in the identification of compounds with improved activity. The most active compound has an IC50 value of 58 mu M against the enzyme. (C) 2007 Elsevier Ltd. All rights reserved.

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页码：380 / 385

页数：6

相关论文

共 36 条

[1]

Community-onset methicillin-resistant Staphylococcus aureus associated with antibiotic use and the cytotoxin Panton-Valentine leukocidin during a furunculosis outbreak in rural Alaska [J].

Baggett, HC ;

Hennessy, TW ;

Rudolph, K ;

Bruden, D ;

Reasonover, A ;

Parkinson, A ;

Sparks, R ;

Donlan, RM ;

Martinez, P ;

Mongkolrattanothai, K ;

Butler, JC .

JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (09) :1565-1573

[2]

Differential recognition of surface proteins in Streptococcus pyogenes by two sortase gene homologs [J].

Barnett, TC ;

Scott, JR .

JOURNAL OF BACTERIOLOGY, 2002, 184 (08) :2181-2191

[3]

Inactivation of the srtA gene in Listeria monocytogenes inhibits anchoring of surface proteins and affects virulence [J].

Bierne, H ;

Mazmanian, SK ;

Trost, M ;

Pucciarelli, MG ;

Liu, G ;

Dehoux, P ;

Jänsch, L ;

Garcia-del Portillo, F ;

Schneewind, O ;

Cossart, P .

MOLECULAR MICROBIOLOGY, 2002, 43 (04) :869-881

[4]

Inactivation of the srtA gene in Streptococcus gordonii inhibits cell wall anchoring of surface proteins and decreases in vitro and in vivo adhesion [J].

Bolken, TC ;

Franke, CA ;

Jones, KF ;

Zeller, GO ;

Jones, CH ;

Dutton, EK ;

Hruby, DE .

INFECTION AND IMMUNITY, 2001, 69 (01) :75-80

[5]

Bacteria as potential tools in bioterrorism, with an emphasis on bacterial toxins [J].

Clarke, SC .

BRITISH JOURNAL OF BIOMEDICAL SCIENCE, 2005, 62 (01) :40-46

[6]

Sortase, a universal target for therapeutic agents against Gram-positive bacteria? [J].

Cossart, P ;

Jonquières, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (10) :5013-5015

[7]

Methicillin-resistant Staphylococcus aureus:: An evolutionary, epidemiologic, and therapeutic odyssey [J].

Deresinski, S .

CLINICAL INFECTIOUS DISEASES, 2005, 40 (04) :562-573

[8]

CONSERVATION OF A HEXAPEPTIDE SEQUENCE IN THE ANCHOR REGION OF SURFACE-PROTEINS FROM GRAM-POSITIVE COCCI [J].

FISCHETTI, VA ;

PANCHOLI, V ;

SCHNEEWIND, O .

MOLECULAR MICROBIOLOGY, 1990, 4 (09) :1603-1605

[9]

The sortase SrtA of Listeria monocytogenes is involved in processing of internalin and in virulence [J].

Garandeau, C ;

Réglier-Poupet, H ;

Dubail, L ;

Beretti, JL ;

Berche, P ;

Charbit, A .

INFECTION AND IMMUNITY, 2002, 70 (03) :1382-1390

[10]

On the role of Staphylococcus aureus sortase and sortase-catalyzed surface protein anchoring in murine septic arthritis [J].

Jonsson, IM ;

Mazmanian, SK ;

Schneewind, O ;

Verdrengh, M ;

Bremell, T ;

Tarkowski, A .

JOURNAL OF INFECTIOUS DISEASES, 2002, 185 (10) :1417-1424

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