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Issue 3-4, 2006
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Establishment of the platform for reverse chemical genetics targeting novel protein–protein interactions

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Abstract

In the “drug discovery” era, proteinprotein interaction modules are becoming the most exciting group of targets for study. Although combinatorial libraries and active natural products are rapidly and systemically being equipped by both for-profit and not-for-profit organizations, complete drug-screening systems have not been achieved. There is a growing need for the establishment of drug discovery assays for highly effective utilization of the collected small molecules on a large scale. To generate drug-screening systems, we plan to identify novel proteinprotein interactions that may participate in human diseases. The interactions have been identified by MS/MS analysis following immunoprecipitation using antibodies prepared from our cDNA projects. The intracellular pathway involving the identified interaction is computationally constructed, which then clarifies its relationship to the candidate disease. The development of reverse chemical genetics based on such information should help us to realize a significant increment in the number of drug discovery assays available for use. In this article, I describe our strategy for drug discovery and then introduce the applicability of fluorescence intensity distribution analysis (FIDA) and the expression-ready constructs called “ORF trap clones” to reverse chemical genetics.

Graphical abstract: Establishment of the platform for reverse chemical genetics targeting novel protein–protein interactions

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Article information


Submitted
12 Dec 2005
Accepted
20 Jan 2006
First published
08 Feb 2006

Mol. BioSyst., 2006,2, 159-164
Article type
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Establishment of the platform for reverse chemical genetics targeting novel proteinprotein interactions

H. Koga, Mol. BioSyst., 2006, 2, 159 DOI: 10.1039/B517589E

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