Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry

Bioorg Med Chem Lett. 2013 Aug 15;23(16):4719-22. doi: 10.1016/j.bmcl.2013.05.066. Epub 2013 May 29.

Abstract

STAT3 (Signal Transducer and Activator of Transcription factor 3) is constitutively active in a wide range of human tumours. Stattic is one of the first non-peptidic small molecules reported to inhibit formation of the STAT3:STAT3 protein dimer complex. A mass spectrometry method has been developed to investigate the binding of Stattic to the un-phosphorylated STAT3βtc (U-STAT3) protein. Alkylation of four cysteine residues has been observed with possible reaction at a fifth which could account for the mechanism of action.

Keywords: Cancer; Mass spectrometry; Protein:protein interaction inhibitor; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / chemistry
  • Amino Acid Sequence
  • Binding Sites
  • Cyclic S-Oxides / chemistry*
  • Dimerization
  • Humans
  • Mass Spectrometry*
  • Models, Molecular
  • Molecular Structure
  • Proteins / chemistry
  • STAT3 Transcription Factor / antagonists & inhibitors

Substances

  • Alkylating Agents
  • Cyclic S-Oxides
  • Proteins
  • STAT3 Transcription Factor
  • stattic