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Curr Opin Chem Biol. 2010 Aug;14(4):481-8. doi: 10.1016/j.cbpa.2010.06.169. Epub 2010 Jul 2.

Intrinsically disordered proteins are potential drug targets.

Author information

1
Department of Chemistry, Georgetown University, 37th & O Streets, NW, Washington, DC 20057, United States. sjm24@georgetown.edu

Abstract

Intrinsically disordered (ID) proteins that lack stable secondary and tertiary structure in substantial regions (or throughout) are prevalent in eukaryotes. They exist as ensembles of rapidly fluctuating structures and many undergo coupled folding and binding reactions. Because ID proteins are overrepresented in major disease pathways they are desirable targets for inhibition; however, the feasibility of targeting proteins without defined structures was unclear. Recently, small molecules have been found that bind to the disordered regions of c-Myc, Abeta, EWS-Fli1, and various peptides. As with structured targets, initial hits were further optimized to increase specificity and affinity. Given the number and biological importance of ID proteins, the ability to inhibit their interactions opens tremendous potential in chemical biology and drug discovery.

PMID:
20598937
PMCID:
PMC2918680
DOI:
10.1016/j.cbpa.2010.06.169
[Indexed for MEDLINE]
Free PMC Article

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