Chemical screening by mass spectrometry to identify inhibitors of anthrax lethal factor

被引:128
作者
Min, DH
Tang, WJ
Mrksich, M
机构
[1] Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
[2] Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA
基金
美国国家科学基金会;
关键词
D O I
10.1038/nbt973
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Mass spectrometry (MS) analysis is applicable to a broad range of biological analytes and has the important advantage that it does not require analytes to be labeled. A drawback of MS methods, however, is the need for chromatographic steps to prepare the analyte, precluding MS from being used in chemical screening and rapid analysis. Here, we report that surfaces that are chemically tailored for characterization by matrix-assisted laser-desorption ionization time-of-flight MS eliminate the need for sample processing and make this technique adaptable to parallel screening experiments. The tailored substrates are based on self-assembled monolayers that present ligands that interact with target proteins and enzymes. We apply this method to screen a chemical library against protease activity of anthrax lethal factor, and report a compound that inhibits lethal factor activity with a K-i of 1.1 muM and blocks the cleavage of MEK1 in 293 cells.
引用
收藏
页码:717 / 723
页数:7
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