Synthesis and characterization of branched phosphopeptides: Prototype consolidated ligands for SH(32) domains

This paper details the solid-phase synthesis by N^α-9-fluorenylmethyloxycarbonyl (Fmoc) chemistry of a series of bivalent consolidated ligands, branched peptides with lengths of 22 to 25 residues. The target peptides were designed to, and in fact do, interact with greater specificity and higher affinity with the SH2 and SH3 domains of Abelson kinase in an SH(32) dual domain construct. Fmoc-O-phospho-L-tyrosine [Fmoc-Tyr(PO₃H₂)-OH] was used to introduce the required phosphotyrosine residues, and Fmoc-N^ε-1-(4,4-dimethyl-2,6-dioxocyclonexylidene)ethyl-L-lysine [Fmoc-Lys(Dde)-OH] was used to introduce a branch point that allowed proper orientation of individual ligands. The resultant product peptides were characterized by amino acid analyses and electrospray mass spectra.