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

Dal Hee Min, Wei Jen Tang, Milan Mrksich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


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 Ki of 1.1 μM and blocks the cleavage of MEK1 in 293 cells.

Original languageEnglish (US)
Pages (from-to)717-723
Number of pages7
JournalNature biotechnology
Issue number6
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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