Orthogonal functionalisation of α-helix mimetics

Org Biomol Chem. 2014 Sep 21;12(35):6794-9. doi: 10.1039/c4ob00915k.

Abstract

α-Helix mediated protein-protein interactions are of major therapeutic importance. As such, the design of inhibitors of this class of interaction is of significant interest. We present methodology to modify N-alkylated aromatic oligoamide α-helix mimetics using 'click' chemistry. The effect is shown to modulate the binding properties of a series of selective p53/hDM2 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Biomimetics
  • Click Chemistry
  • Humans
  • Inhibitory Concentration 50
  • Myeloid Cell Leukemia Sequence 1 Protein / chemistry
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • Proteomics / methods
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-mdm2 / chemistry*
  • Solvents / chemistry
  • Surface Properties
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / chemistry*
  • bcl-X Protein / chemistry

Substances

  • Amides
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Solvents
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • bcl-X Protein
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2