High-Throughput Screening of Metalloproteases Using Small Molecule Microarrays

  • Mahesh Uttamchandani
Part of the Methods in Molecular Biology book series (MIMB, volume 632)


The promise of rapid and cost-effective drug screening assays on solid support is one that may now be realized with the advent of small molecule microarrays. Many of the initial hurdles in library design and microarray fabrication have been overcome over the last decade, allowing this platform to become more accessible to researchers across both the academic and industrial spheres. Beyond pharmaceutical screening, microarrays reveal quantitative ligand-binding signatures that in the form of protein fingerprints provide a means to discriminate between closely related proteins. The value of protein fingerprinting in drug discovery is also highlighted through the identification of ligands that not only offer good potency, but also good selectivity. Herein, we describe the method for high-throughput screening and profiling of metalloproteases on small molecule microarrays. Metalloproteases are an important class of proteins, which are implicated in the pathogenicity of certain microbes and in the progression of cancer. We have introduced a novel two-colour labelling and application approach that directly elucidates functional ligands, reducing the burden of downstream revalidation of identified hits.

Key words

Small molecule microarray High-throughput screening Metalloproteases Hydroxa­mate peptides Two-colour labelling/application 



Funding support is acknowledged from DSO National Laboratories and the National University of Singapore.


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mahesh Uttamchandani
    • 1
    • 2
  1. 1.Defense Medical and Environmental Research Institute (DMERI), DSO National LaboratoriesSingaporeSingapore
  2. 2.Department of ChemistryNational University of SingaporeSingaporeSingapore

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