Solubilizing Trityl-Type Tag To Synthesize Asx/Glx-Containing Peptides

A novel solubilizing tag system for Asp/Asn/Glu/Gln-containing peptides is described. In this method, an Asp/GluDbz-Cys-NH₂]-containing peptide (Dbz: 3,4-diaminobenzoic acid) is first synthesized through fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis. The solubilizing moiety containing an oligo-Lys group is then attached to the peptide in hexafluoroisopropanol through a trityl anchor to afford a hydrophilic tagged peptide. To detach the solubilizing tag, the Dbz moiety of the tagged peptide is activated with NaNO₂, and the Asp/Asn/Glu/Gln-containing peptide is obtained through hydrolysis or ammonolysis. This synthetic approach proved to be compatible with native chemical ligation, and amyloid β-protein 1–42 was successfully synthesized by the solubilizing-tag-aided native chemical ligation–desulfurization method.