Journal
ACS CHEMICAL BIOLOGY
Volume 3, Issue 11, Pages 677-692Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cb8001792
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Funding
- National Institutes of Health [CA118631]
- merican-Australian Association's Alcoa Foundation
- Canadian Institutes of Health Research
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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.
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