Rational drug design via intrinsically disordered protein

Yugong Cheng, Tanguy LeGall, Christopher J. Oldfield, James P. Mueller, Ya Yue J. Van, Pedro Romero, Marc S. Cortese, Vladimir N. Uversky, A. Keith Dunker

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

Despite substantial increases in research funding by the pharmaceutical industry, drug discovery rates seem to have reached a plateau or perhaps are even declining, suggesting the need for new strategies. Protein-protein interactions have long been thought to provide interesting drug discovery targets, but the development of small molecules that modulate such interactions has so far achieved a low success rate. In contrast to this historic trend, a few recent successes raise hopes for routinely identifying druggable protein-protein interactions. In this Opinion article, we point out the importance of coupled binding and folding for protein-protein signalling interactions generally, and from this and associated observations, we develop a new strategy for identifying protein-protein interactions that would be particularly promising targets for modulation by small molecules. This novel strategy, based on intrinsically disordered protein, has the potential to increase significantly the discovery rate for new molecule entities.

Original languageEnglish (US)
Pages (from-to)435-442
Number of pages8
JournalTrends in Biotechnology
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2006

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering

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    Cheng, Y., LeGall, T., Oldfield, C. J., Mueller, J. P., Van, Y. Y. J., Romero, P., Cortese, M. S., Uversky, V. N., & Dunker, A. K. (2006). Rational drug design via intrinsically disordered protein. Trends in Biotechnology, 24(10), 435-442. https://doi.org/10.1016/j.tibtech.2006.07.005