title: Efficient semisynthesis of a tetraphosphorylated analogue of the Type I TGFbeta receptor.
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.
authors.affiliation: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York 10021, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Flavell
authors.forename: Morgan
authors.initials: M
authors.lastname: Huse
authors.forename: Mike
authors.initials: M
authors.lastname: Goger
authors.forename: Michelle
authors.initials: M
authors.lastname: Trester-Zedlitz
authors.forename: John
authors.initials: J
authors.lastname: Kuriyan
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
mesh_terms: D030201:Activin Receptors, Type I / Q000138:chemical synthesis*; D020816:Amino Acid Motifs; D004591:Electrophoresis, Polyacrylamide Gel; D010750:Phosphoproteins / Q000138:chemical synthesis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D012117:Resins, Synthetic; D012694:Serine; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013912:Threonine
chemical_list: D010750:Phosphoproteins; D018125:Receptors, Transforming Growth Factor beta; D012117:Resins, Synthetic; D013912:Threonine; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I