Lithium chloride: An efficient additive for the synthesis of α-conotoxin PnIA(A10L) in the Fmoc solid phase strategy

Abstract

PnIA(A10L) is a potential molecule for the diagnosis and treatment of α7 nAChR related disease, but its preparation is often limited by the efficiency of standard Fmoc solid phase peptide synthesis (SPPS). In this work, we proved that the chaperone salt LiCl was an effective additive to improve the synthesis efficiency of PnIA(A10L) by using Fmoc/tBu SPPS. Firstly, we screened an appropriate Fmoc deprotection reagent 2-methylpiperidine for PnIA(A10L) synthesis using LiCl. Secondly, the positive promotion of LiCl in amino acid condensation and Fmoc deprotection was confirmed in the synthesis of PnIA(A10L). Finally, the effect of dosage of LiCl on the synthesis efficiency of PnIA(A10L) suggested when the dosage of LiCl was less than 4 equivalent (equiv.) the resin loading, LiCl could significantly improve the synthesis efficiency, and the 2 equiv. was optimal dosage. The optimized addition of LiCl method reported here will provide a simple and practical strategy for the synthesis of PnIA(A10L) and promote the application of LiCl in difficult peptide synthesis.