Combined mass spectrometry and dynamic chemistry approach to identify metalloenzyme inhibitors

被引：36

作者：

Lienard, Benoft M. R.

Selevsek, Nathalie

Oldham, Neil J.

Schofield, Christopher J.

机构：

[1] Chemistry Research Laboratory, Oxford OX1 3TA, Mansfield Road

[2] Department of Biochemical Engineering, Saarland University

来源：

CHEMMEDCHEM | 2007年 / 2卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

Disulfide exchange; Dynamic hemistry; Mass spectrometry; Metallo-β-; lactamase; Structure-activity relationships;

D O I：

10.1002/cmdc.200600250

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An approach combining thiol based dynamic chemistry and MS was used to explore the SAR of a metallo-beta-lactamase. Analogues of preferentially binding disulfides were synthesized and shown to be potent inhibitors.

引用

页码：175 / +

页数：6

共 20 条

[1] Mass spectrometry of macromolecular assemblies: preservation and dissociation [J].

Benesch, JL ;

Robinson, CV .

CURRENT OPINION IN STRUCTURAL BIOLOGY, 2006, 16 (02) :245-251

[2] Generation of Bis-cationic heterocyclic inhibitors of Bacillus subtilis HPr kinase/phosphatase from a ditopic dynamic combinatorial library [J].

Bunyapaiboonsri, T ;

Ramström, H ;

Ramström, O ;

Haiech, J ;

Lehn, JM .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (26) :5803-5811

[3]

Bunyapaiboonsri T, 2001, CHEMBIOCHEM, V2, P438

[4] A FUNCTIONAL CLASSIFICATION SCHEME FOR BETA-LACTAMASES AND ITS CORRELATION WITH MOLECULAR-STRUCTURE [J].

BUSH, K ;

JACOBY, GA ;

MEDEIROS, AA .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (06) :1211-1233

[5] Tethering: Fragment-based drug discovery [J].

Erlanson, DA ;

Wells, JA ;

Braisted, AC .

ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 2004, 33 :199-223

[6] Investigation of intact protein complexes by mass spectrometry [J].

Heck, AJR ;

van den Heuvel, RHH .

MASS SPECTROMETRY REVIEWS, 2004, 23 (05) :368-389

[7] Ligand amplification in a dynamic combinatorial glycopeptide library [J].

Hotchkiss, T ;

Kramer, HB ;

Doores, KJ ;

Gamblin, DP ;

Oldham, NJ ;

Davis, BG .

CHEMICAL COMMUNICATIONS, 2005, (34) :4264-4266

[8] Expanding diversity in dynamic combinatorial libraries: simultaneous exchange of disulfide and thioester linkages [J].

Leclaire, J ;

Vial, L ;

Otto, S ;

Sanders, JKM .

CHEMICAL COMMUNICATIONS, 2005, (15) :1959-1961

[9]

Loo JA, 1997, MASS SPECTROM REV, V16, P1

[10] Analysis of the importance of the metallo-β-lactamase active site loop in substrate binding and catalysis [J].

Moali, C ;

Anne, C ;

Lamotte-Brasseur, J ;

Groslambert, S ;

Devreese, B ;

Van Beeumen, J ;

Galleni, M ;

Frère, JM .

CHEMISTRY & BIOLOGY, 2003, 10 (04) :319-329

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