Evaluation of the Final Deprotection System for the Solid-Phase Synthesis of Tyr(SO₃H)-Containing Peptides with 9-Fluorenylmethyloxycarbonyl (Fmoc)-Strategy and Its Application to the Synthesis of Cholecystokinin (CCK)-12

Abstract

Acidolytic deprotection and cleavage conditions for an acid-labile Tyr(SO₃H)-containing peptide were systematically examined with respect to acid, temperature, and scavenger. The 90% aqueous trifluoroacetic acid (TFA)-based reagent systems (90% aqueous TFA/m-cresol and 90% aqueous TFA/m-cresol/2-methylindole) at 4°C were found to minimize the deterioration of Tyr(SO₃Na) in the peptide. The latter deprotection/cleavage system was applied to the 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase synthesis of cholecystokinin (CCK)-12 on an acid-labile PAL-linked support (PAL=peptide amide linker), with Fmoc-Tyr(SO₃Na)-OH as a building block.