Efficient semisynthesis of a tetraphosphorylated analogue of the Type I TGFbeta receptor

Org Lett. 2002 Jan 24;4(2):165-8. doi: 10.1021/ol016859i.

Abstract

[structure: see text] Semisynthesis of an active tetraphosphorylated analogue of the Type I TGFbeta receptor is reported. An efficient native chemical ligation protocol was developed to link a tetraphosphopeptide and a recombinant receptor fragment. Synthesis of the peptide alpha-thioester on a 4-sulfamylbutyryl resin was optimized following the characterization of a major side reaction and subsequent substitution of norleucine for methionine in the peptide sequence. These optimized protocols will be applicable to the semisynthesis of related protein kinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors, Type I / chemical synthesis*
  • Amino Acid Motifs
  • Electrophoresis, Polyacrylamide Gel
  • Phosphoproteins / chemical synthesis
  • Phosphorylation
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta
  • Resins, Synthetic
  • Serine
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Threonine

Substances

  • Phosphoproteins
  • Receptors, Transforming Growth Factor beta
  • Resins, Synthetic
  • Threonine
  • Serine
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I