SYNTHESIS OF THE Mdm2 RING FINGER DOMAIN BY COMBINED CONVERGENT AND NATIVE CHEMICAL LIGATION METHODS

摘要

The RING finger domain of Mdm2, located at the C-terminal part of the protein, is necessary for the regulation of the tumour-suppressor protein p53 and therefore it is an important target for studying its interaction with small anticancer drug candidates. Due to the presence of multiple cysteine residues, the synthesis of such small proteins is difficult to be performed using recombinant techniques. The 48-residue Mdm2 peptide (Fig. 1) has been previously synthesized by sequential condensation of protected fragments on 2-chlorotrityl resin . Here, we report the efficient synthesis of this peptide by applying a combination of Fmoc-based convergent synthesis (CPS) and native chemical ligation (NCL).