Backbone Amide Linker Strategies for the Solid-Phase Synthesis of C - Terminal Modified Peptides

This chapter describes backbone amide linker (BAL) strategies for the N α-Fmoc solid-phase synthesis of C-terminal modified peptides. Most solid-phase protocols for the assembly of such peptides have limited generality, because they rely on the C α-carboxyl for attachment to the solid support. In the BAL approach, the growing peptide chain is anchored through a backbone nitrogen, thus allowing significant flexibility for chemical modification of the C-termini. In effect, any peptide containing C-terminal variations can be prepared in overall good purity and yield, with minimal side reactions, by using one or more of three variations (original and two modifications) of the BAL strategy.