Multivalent helix mimetics for PPI-inhibition. Issue 1 (13th November 2014)

• Record Type: Journal Article
• Authors: Barnard, Anna; Miles, Jennifer A.; Burslem, George M.; Barker, Amy M.; Wilson, Andrew J.
• Is Part Of: Organic & biomolecular chemistry. Volume 13:Issue 1(2015)
• Page Start: 258
• Page End: 264
• Publication Date: 2014-11-13
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c4ob02066a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A multivalent helix mimetic is developed that inhibits the p53/ h DM2 and induces dimerization/aggregation of its target – h DM2. 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/ h DM2 and establish that protein dimerisation is promoted, rather than enhanced binding resulting from a higher effective concentration of the ligand.