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

Craig R. Braun; Julian Mintseris; Evripidis Gavathiotis; Gregory H. Bird; Steven P. Gygi; Loren D. Walensky

doi:10.1016/j.chembiol.2010.09.015

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

Craig R. Braun, Julian Mintseris, Evripidis Gavathiotis, Gregory H. Bird, Steven P. Gygi, Loren D. Walensky

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1325-1333
Number of pages	9
Journal	Chemistry and Biology
Volume	17
Issue number	12
DOIs	https://doi.org/10.1016/j.chembiol.2010.09.015
State	Published - Dec 22 2010
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2010.09.015

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title = "Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome",

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.",

author = "Braun, {Craig R.} and Julian Mintseris and Evripidis Gavathiotis and Bird, {Gregory H.} and Gygi, {Steven P.} and Walensky, {Loren D.}",

note = "Funding Information: We thank E. Smith for figure design and editorial assistance. This work was supported by NIH grant 5P01CA92625, 1R01GM090299, and a Stand Up to Cancer Innovative Research Grant to L.D.W., and a National Sciences and Engineering Research Council of Canada postgraduate scholarship to C.R.B. L.D.W. is a consultant and scientific advisory board member for Aileron Therapeutics. ",

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AU - Gavathiotis, Evripidis

AU - Bird, Gregory H.

AU - Gygi, Steven P.

AU - Walensky, Loren D.

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

Abstract

ASJC Scopus subject areas

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