Multivalent helix mimetics for PPI-inhibition

Org Biomol Chem. 2015 Jan 7;13(1):258-64. doi: 10.1039/c4ob02066a.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology*
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology*
  • Models, Molecular
  • Protein Binding / drug effects
  • Protein Conformation
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Amides
  • CNBP protein, human
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53