New syntheses of tetrazolylmethylphenylalanine and O-malonyltyrosine as pTyr mimetics for the design of STAT3 dimerization inhibitors

Bioorg Med Chem Lett. 2007 Jul 15;17(14):3943-6. doi: 10.1016/j.bmcl.2007.04.107. Epub 2007 May 3.

Abstract

Investigation within the pTyr-binding pocket of the STAT3 SH2 domain led us to develop a novel synthesis of two pTyr mimetics, l-tetrazolylmethylphenylalanine (l-Tmp) and l-O-malonyltyrosine (l-OMT), that were next incorporated in a high affinity ligand of STAT3 SH2 domain. Biological evaluation of peptidomimetics on STAT3 dimerization identified l-OMT as the first non-phosphorus pTyr mimetic so far reported against STAT3 SH2 domain, harboring an activity similar to that of the Pmp-containing reference peptidomimetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dimerization
  • Drug Design
  • Enzyme-Linked Immunosorbent Assay
  • Molecular Mimicry*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / chemical synthesis*
  • Phenylalanine / pharmacology
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / chemistry*
  • Tyrosine / analogs & derivatives
  • Tyrosine / chemical synthesis*
  • Tyrosine / pharmacology

Substances

  • STAT3 Transcription Factor
  • Tyrosine
  • Phenylalanine