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Journal of Biomolecular Screening
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Article

Screening for Ligands Using a Generic and High-Throughput Light-Scattering-Based Assay

Guillermo A. Senisterra1*, Eugene Markin2, Ken Yamazaki1, Raymond Hui1, Masoud Vedadi1, Donald E. Awrey3

1 Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada
2 Allied Research International, Inc., Toronto, Ontario, Canada
3 Campbell Family Institute for Breast Cancer Research Therapeutics, Toronto, Ontario, Canada

* To whom correspondence should be addressed. E-mail: g.senisterra{at}utoronto.ca..


  Abstract

Rapid identification of small molecules that interact with protein targets using a generic screening method greatly facilitates the development of therapeutic agents. The authors describe a novel method for performing homogeneous biophysical assays in a high-throughput format. The use of light scattering as a method to evaluate protein stability during thermal denaturation in a 384-well format yields a robust assay with a low frequency of false positives. This novel method leads to the identification of interacting small molecules without the addition of extraneous fluorescent probes. The analysis and interpretation of data is rapid, with sensitivity for protein stability comparable to differential scanning calorimetry. The authors propose potential uses in drug discovery, structural genomics, and functional genomics as a method to evaluate small-molecule interactions, identify natural cofactors that stabilize target proteins, and identify natural substrates and products for previously uncharacterized protein targets.

Key Words: light scattering, protein stabilization, binding, aggregation

First published on November 7, 2006, doi:10.1177/1087057106294699

Journal of Biomolecular Screening 2006;11:940.

A more recent version of this article appeared on December 1, 2006

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