Solid-phase synthesis of Stat3 inhibitors incorporating O-carbamoylserine and O-carbamoylthreonine as glutamine mimics

Bioorg Med Chem Lett. 2007 Feb 1;17(3):654-6. doi: 10.1016/j.bmcl.2006.10.099. Epub 2006 Nov 6.

Abstract

O-Carbamoylserine and O-carbamoylthreonine are glutamine analogues that were incorporated into a Stat3 inhibitory peptide to probe the requirements of Gln at the pY+3 position. Fmoc-Ser-NHBn and Fmoc-Thr-NHBn were converted to nitrophenyl carbonates and were attached to Rink resin via a side-chain carbamate linkage. After assembly of the peptide, acid treatment resulted in O-carbamoylserine and O-carbamoylthreonine-containing peptides. The order of affinity for Stat3 was Gln > Ser(CONH2) >> Thr(CONH2) suggesting a relatively tight binding pocket for the side chain of glutamine.

Publication types

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

MeSH terms

  • Crystallography, X-Ray
  • Glutamine / pharmacology*
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Molecular Mimicry
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • Serine / analogs & derivatives*
  • Serine / pharmacology
  • Threonine / analogs & derivatives*
  • Threonine / chemistry
  • src Homology Domains / drug effects

Substances

  • Indicators and Reagents
  • O-carbamoylthreonine
  • STAT3 Transcription Factor
  • Glutamine
  • Threonine
  • O-carbamylserine
  • Serine