title: Synthesis of linear and cyclic phosphopeptides as ligands for the N-terminal SH2-domain of protein tyrosine phosphatase SHP-1.
abstract: Linear and cyclic phosphopeptides related to the pY2267 binding site of the epithelial receptor tyrosine kinase Ros have been synthesized as ligands for the amino-terminal SH2 (src homology) domain of protein tyrosine phosphatase SHP-1. The synthesis was accomplished by Fmoc-based solid-phase methodology using side-chain unprotected phosphotyrosine for the linear and mono-benzyl protected phosphotyrosine for the cyclic peptides. According to molecular modelling, the incorporation of a glycine residue between Lys (position pY-1 relative to phosphotyrosine) and Asp or Glu (position pY+2) was recommended for the cyclic candidates. The preparation of these peptides was successfully performed by the incorporation of a Fmoc-Xxx(Gly-OAll)-OH (Xxx = Asp, Glu) dipeptide building block that was prepared in solution prior to SPPS. The cyclization was achieved with PyBOP following Alloc/OAll-deprotection. This study demonstrates the usefulness of allyl-type protecting groups for the generation of side-chain cyclized phosphopeptides. Alloc/OAll-deprotection and cyclization are compatible with phosphorylated tyrosine.
authors.affiliation: Institute of Biochemistry and Biophysics, Biological-Pharmaceutical Faculty, Friedrich-Schiller-University, Philosophenweg 12, D-07743 Jena, Germany. b4imdi@rz.uni-jena.de
authors.forename: Diana
authors.initials: D
authors.lastname: Imhof
authors.forename: Doreen
authors.initials: D
authors.lastname: Nothmann
authors.forename: Mohammad Safa
authors.initials: MS
authors.lastname: Zoda
authors.forename: Kornelia
authors.initials: K
authors.lastname: Hampel
authors.forename: Jenny
authors.initials: J
authors.lastname: Wegert
authors.forename: Frank D
authors.initials: FD
authors.lastname: Böhmer
authors.forename: Siegmund
authors.initials: S
authors.lastname: Reissmann
mesh_terms: D002851:Chromatography, High Pressure Liquid; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D013058:Mass Spectrometry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism; D010748:Phosphopeptides / Q000138:chemical synthesis* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D010456:Peptides, Cyclic; D010748:Phosphopeptides; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases