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: 6.65). 12/2010; 17(12):1325-33. DOI: 10.1016/j.chembiol.2010.09.015
Source: PubMed


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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Available from: Evripidis Gavathiotis, Sep 29, 2015
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    • "Stabilized α-helix, SAH, is a stapled peptide to p53 that has been shown to prevent p53-MDM4 binding, enabling activation of p53 response and tumor growth suppression both in vitro and in vivo models [104]. Recently, engineered photoreactive stapled BH3 peptide helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a new scope for targeted drug design for the BCL-2 family targets [105]. Visualizing potential sites on Gabs for similar stapled peptides can provide fascinating insights into protein-binding disruption. "
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