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.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Braun
authors.forename: Julian
authors.initials: J
authors.lastname: Mintseris
authors.forename: Evripidis
authors.initials: E
authors.lastname: Gavathiotis
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Bird
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Loren D
authors.initials: LD
authors.lastname: Walensky
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2