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Small Molecule Modulators of Transcription
Hans-Dieter Arndt Dr.,
Hans-Dieter Arndt Dr.
Universität Dortmund, Fachbereich Chemie, Otto-Hahn-Str. 6, 44221 Dortmund, Germany
Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Str. 11, 44227 Dortmund, Germany, Fax: (+49) 231-133-2498
Search for more papers by this authorHans-Dieter Arndt Dr.,
Hans-Dieter Arndt Dr.
Universität Dortmund, Fachbereich Chemie, Otto-Hahn-Str. 6, 44221 Dortmund, Germany
Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Str. 11, 44227 Dortmund, Germany, Fax: (+49) 231-133-2498
Search for more papers by this authorGraphical Abstract
Small can do too: Recent research on transcriptional factors has uncovered small-molecule ligands that are able to modulate gene transcription by interacting with multiprotein complexes. Some of these compounds bind to different sites on the target proteins and therefore exert different functions. The picture shows the association of the HDM2 protein (bronze) with the tumor suppressor p53 (green), and two small molecules that influence p53 function positively.
Abstract
Signal transduction cascades ultimately trigger transcriptional programs that are executed by transcription factors interacting with coactivator or corepressor proteins in large multi-protein complexes. Despite the difficulties associated with discovering and verifying potent antagonists (or agonists) of protein–protein interaction events, several small molecules have been identified within the last few years that modulate transcription by directly interacting with transcriptional proteins. Some of these small molecules display surprising selectivity and some even show efficacy in vivo. This review summarizes the current status in this developing field to illustrate the emerging opportunities in the chemical biology of transcription.
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