3] Cleavage methods following Boc-based solid-phase peptide synthesis

Abstract

[3] Cleavage methods following Boc-based solid-phase peptide synthesis In solid-phase peptide synthesis (SPPS) using Boc (tert-butyloxycar bonyl) amino acids, peptide chains are linked to the resin supports as benzyl esters or by bonds of similar chemical stability, and side-chain functional groups are protected by groups of similar reactivity. Although anhydrous hydrogen fluoride (HF) is an inconvenient (it dissolves glass, is volatile) and toxic reagent, it has been used successfully in SPPS and is the cleavage reagent of choice in most cases. Methods have been developed to overcome the limitations of HF cleavage—such as unwanted side reactions with certain amino acids. If equipment for handling HF is not available, peptide-resins may be cleaved by using trifluoromethanesulfonic acid (TFMSA) or trifluoromethanesulfonic acid trimethylsilyl ester (TMSOTf), although these reagents may cause serious side reactions with some peptides. Much of the versatility of the Merrifield system of Boc SPPS lies in the fact that different reagents can be used to cleave the finished peptide from the resin, thus, yielding a variety of final products.