Design and applications of bifunctional small molecules: Why two heads are better than one

Timothy W. Corson, Nicholas Aberle, Craig M. Crews

Research output: Contribution to journalReview article

99 Scopus citations

Abstract

Induction of protein - protein interactions is a daunting challenge, but recent studies show promise for small molecules that specifically bring two or more protein molecules together for enhanced or novel biological effect. The first such bifunctional molecules were the rapamycin- and FK506-based "chemical inducers of dimerization", but the field has since expanded with new molecules and new applications in chemical genetics and cell biology. Examples include coumermycin-mediated gyrase B dimerization, proteolysis targeting chimeric molecules (PROTACs), drug hybrids, and strategies for exploiting multivalency in toxin binding and antibody recruitment. This Review discusses these and other advances in the design and use of bifunctional small molecules and potential strategies for future systems.

Original languageEnglish (US)
Pages (from-to)677-692
Number of pages16
JournalACS chemical biology
Volume3
Issue number11
DOIs
StatePublished - Nov 21 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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