Evaluation of the Final Deprotection System for the Solid-Phase Synthesis of Tyr(SO3 H)-Containing PeptiDes with 9-Fluorenylmethyloxycarbonyl (Fmoc)-Strategy and Its Application to the Synthesis of Cholecystokinin (CCK)-121)

Abstract

Acidolytic Deprotection and cleavage conditions for an acid-labile Tyr(SO3 H)-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(SO3 Na) 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(SO3 Na)-OH as a building block. © 1993, The Pharmaceutical Society of Japan. All rights reserved.