Solid-phase synthesis with tris(alkoxy)benzyl backbone amide linkage (BAL)

Solid-phase synthesis has been applied successfully for the preparation of peptides, small proteins, oligonucleotides, and small organic molecules. A crucial part of the overall synthesis plan is the choice of an appropriate "handle" (linker) for attachment to the support. Here we describe a novel and general concept for solid-phase synthesis that involves attachment of a backbone amide nitrogen to an appropriate handle. This backbone amide linker (BAL) approach allows for the preparation of C-terminal-modified and cyclic peptides, small organic molecules, and modified amino sugars, as well as combinatorial synthesis applications.