Coordination complex SH2 domain proteomimetics: an alternative approach to disrupting oncogenic protein-protein interactions

Chem Commun (Camb). 2010 Feb 14;46(6):892-4. doi: 10.1039/b919608k. Epub 2009 Dec 1.

Abstract

We report the first application of coordination complexes as functional proteomimetics of the Src homology 2 (SH2) phosphopeptide-binding domain. As a proof-of-concept, functionalized bis-dipicolylamine (BDPA) copper(ii) complexes are shown to disrupt oncogenic Stat3-Stat3 protein complexes and elicit promising anti-tumour activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amino Acid Sequence
  • Animals
  • Coordination Complexes / chemistry*
  • Copper / chemistry
  • ErbB Receptors / chemistry
  • ErbB Receptors / metabolism
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Picolinic Acids / chemistry
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • STAT3 Transcription Factor / chemistry
  • STAT3 Transcription Factor / metabolism
  • src Homology Domains*

Substances

  • 2,2'-dipicolylamine
  • Amines
  • Coordination Complexes
  • Picolinic Acids
  • STAT3 Transcription Factor
  • Copper
  • ErbB Receptors