Design and applications of bifunctional small molecules

Why two heads are better than one

Timothy Corson, Nicholas Aberle, Craig M. Crews

Research output: Contribution to journalArticle

89 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Dimerization
Molecules
Proteins
Tacrolimus
Sirolimus
Proteolysis
Cell Biology
Cytology
Antibodies
Pharmaceutical Preparations
coumermycin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Design and applications of bifunctional small molecules : Why two heads are better than one. / Corson, Timothy; Aberle, Nicholas; Crews, Craig M.

In: ACS Chemical Biology, Vol. 3, No. 11, 21.11.2008, p. 677-692.

Research output: Contribution to journalArticle

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