Fig. 2. Synthetic strategy for the synthesis of the Bcr-Abl SH2 domain. The N- and C-terminal fragments are in red and blue, respectively, and are synthesized via solid phase peptide synthesis (SPPS). The N-terminal peptide 1 corresponds to the biotinylated Bcr-Abl SH2 domain (138–197) with C-terminal MeDbz linker, which is activated to MeNbz on resin. After cleavage from the resin, the resulting peptide 2 can undergo native chemical ligation (NCL) with the cysteine (Cys)-containing peptide 3 to yield polypeptide 4. Subsequent desulfurization of this Cys variant of Bcr-Abl SH2 (4) provides the final SH2 domain (5). MeDbz: 3-amino-4-(methylamino)benzoic acid; MeNbz: N-acyl-N′-methylacylurea; NCL: native chemical ligation.