Journal
CHEMICAL SOCIETY REVIEWS
Volume 40, Issue 8, Pages 4286-4294Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c1cs15050b
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The human body is comprised of several hundred distinct cell types that all share a common genomic template. This diversity arises from regulated expression of individual genes. The first critical step in this process is transcription and is governed by a large number of transcription factors. Small molecules that can alter transcription hold tremendous utility as chemical probes and therapeutics. To fully realize their potential, however, artificial transcription factors must be able to orchestrate protein recruitment at gene promoters just like their natural counterparts. This tutorial review surveys the discovery of small ligands (drug-like molecules and short peptides) that bind transcriptional coregulatory proteins, and thus comprise one of the two essential characteristics of a transcription factor. By joining these ligands to DNA-targeting moieties, one can construct a bifunctional molecule that recruits its protein target to specific genes and controls gene transcription.
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