title: Multivalent helix mimetics for PPI-inhibition.
abstract: The exploitation of multivalent ligands for the inhibition of protein-protein interactions has not yet been explored as a supramolecular design strategy. This is despite the fact that protein-protein interactions typically occur within the context of multi-protein complexes and frequently exploit avidity effects or co-operative binding interactions to achieve high affinity interactions. In this paper we describe preliminary studies on the use of a multivalent N-alkylated aromatic oligoamide helix mimetic for inhibition of p53/hDM2 and establish that protein dimerisation is promoted, rather than enhanced binding resulting from a higher effective concentration of the ligand.
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. A.J.Wilson@leeds.ac.uk.
authors.forename: Anna
authors.initials: A
authors.lastname: Barnard
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Miles
authors.forename: George M
authors.initials: GM
authors.lastname: Burslem
authors.forename: Amy M
authors.initials: AM
authors.lastname: Barker
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wilson
mesh_terms: D000478:Alkylation; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000577:Amides; C433227:CNBP protein, human; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53