Efficient semisynthesis of a tetraphosphorylated analogue of the Type I TGFbeta receptor.
[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.
Flavell
Robert R
RR
Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York 10021, USA.
Huse
Morgan
M
Goger
Mike
M
Trester-Zedlitz
Michelle
M
Kuriyan
John
J
Muir
Tom W
TW
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
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