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Isr J Chem. 2013 Aug;53(8):588-595.

Small molecule probes to target the human Mediator complex.

Author information

1
Dept. of Chemistry, Yale University, New Haven, CT 06520 USA.
2
Dept. of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303 USA.

Abstract

The human Mediator complex is a central integrator for transcription and represents a primary interface that allows DNA-binding transcription factors to communicate their regulatory signals to the RNA polymerase II enzyme. Because Mediator is dynamic both in terms of subunit composition and structure, it presents challenges as a target for small molecule probes. Moreover, little high-resolution structural information exists for Mediator. Its global requirement for transcription, as well as its distinct, transcription factor specific interaction surfaces, however, suggest that development of probes that bind specific Mediator subunits might enable gene- and pathway-specific modulation of transcription. Here we provide a brief overview of the Mediator complex, highlighting biological and structural features that make it an attractive target for molecular probes. We then outline several chemical strategies that might be effective for targeting the complex.

KEYWORDS:

CDK8 module; Mediator complex; gene expression; probe discovery

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