title: Exploration of the HIF-1α/p300 interface using peptide and Adhiron phage display technologies.
abstract: The HIF-1α/p300 protein-protein interaction plays a key role in tumor metabolism and thus represents a high value target for anticancer drug-development. Although several studies have identified inhibitor candidates using rationale design, more detailed understanding of the interaction and binding interface is necessary to inform development of superior inhibitors. In this work, we report a detailed biophysical analysis of the native interaction with both peptide and Adhiron phage display experiments to identify novel binding motifs and binding regions of the surface of p300 to inform future inhibitor design.
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. t.a.edwards@leeds.ac.uk.
authors.forename: Hannah F
authors.initials: HF
authors.lastname: Kyle
authors.forename: Kate F
authors.initials: KF
authors.lastname: Wickson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stott
authors.forename: George M
authors.initials: GM
authors.lastname: Burslem
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Breeze
authors.forename: Christian
authors.initials: C
authors.lastname: Tiede
authors.forename: Darren C
authors.initials: DC
authors.lastname: Tomlinson
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Warriner
authors.forename: Adam
authors.initials: A
authors.lastname: Nelson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wilson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Edwards
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D050881:E1A-Associated p300 Protein / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D060066:Protein Interaction Maps / Q000187:drug effects; D017433:Protein Structure, Secondary
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019151:Peptide Library; D010455:Peptides; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human