Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome.

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Chemistry & biology (Impact Factor: 6.52). 12/2010; 17(12):1325-33. DOI: 10.1016/j.chembiol.2010.09.015
Source: PubMed

ABSTRACT Defining protein interactions forms the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. To harness the robust binding affinity and selectivity of structured peptides for interactome discovery, we engineered photoreactive stapled BH3 peptide helices that covalently capture their physiologic BCL-2 family targets. The crosslinking α helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a critical link between interactome discovery and targeted drug design.

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