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Printing Proteins as Microarrays for High-Throughput Function Determination
Gavin MacBeath,1*Stuart L. Schreiber2
Systematic efforts are currently under way to construct
defined sets of cloned genes for high-throughput expression and
purificationof recombinant proteins. To facilitate subsequent studies
of proteinfunction, we have developed miniaturized assays that
accommodateextremely low sample volumes and enable the rapid,
simultaneousprocessing of thousands of proteins. A high-precision
robot designedto manufacture complementary DNA microarrays was used to
spotproteins onto chemically derivatized glass slides at extremelyhigh spatial densities. The proteins attached covalently to theslide
surface yet retained their ability to interact specificallywith other
proteins, or with small molecules, in solution. Threeapplications for
protein microarrays were demonstrated: screeningfor protein-protein
interactions, identifying the substrates ofprotein kinases, and
identifying the protein targets of smallmolecules.
1 Center for Genomics Research, Harvard
University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
2 Howard Hughes Medical Institute (HHMI), Department
of Chemistry and Chemical Biology, Harvard University, 12 Oxford
Street, Cambridge, MA 02138, USA.
*
To whom correspondence should be addressed. E-mail:
gavin_macbeath{at}harvard.edu
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