JOURNAL ARTICLE

Multivalent helix mimetics for PPI-inhibition

Anna Barnard, Jennifer A Miles, George M Burslem, Amy M Barker, Andrew J Wilson
Organic & Biomolecular Chemistry 2015 January 7, 13 (1): 258-64
25408290
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.

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