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Small‐Molecule Probes to Target the Human Mediator Complex
Author(s) -
Phillips Andrew J.,
Taatjes Dylan J.
Publication year - 2013
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.201300039
Subject(s) - chemistry , mediator , molecule , small molecule , nanotechnology , biophysics , microbiology and biotechnology , biochemistry , organic chemistry , biology , materials science
The human Mediator complex is a central integrator for transcription 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 factorspecific 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.