3.2 Linkers The purpose of the link

3.2 Linkers The purpose of the linker (or handle) is to provide a reversible linkage between the synthetic peptide chain and the solid support, and to protect the C-terminal a-carboxyl group during the process of chain extension. The choice of linker determines the C-terminal functional group in the final product. Most linkers are designed to release peptide acids or amides upon treatment with TFA, with the concentration of TFA required to effect cleavage dictating whether the product is released in a fully deprotected form or still retaining the acid-sensitive side-chain protecting groups. Linkers are also available in which the peptide-resin linkage is cleaved with nucleophiles, used for the preparation of C-terminally modified peptides such as peptide esters and secondary amides (see Chapter 6, Section 1.2), and by light, which are used for applications such as one-bead-one-compound libraries. The linkers most frequently used in Fmoc/tBu SPPS are listed in Table 3; thoserecommended for the routine synthesis of peptide acids and carboxamides are highlighted.