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 a
nd general concept for solid-phase synthesis that involves attachment of a
backbone amide nitrogen to an appropriate handle. This backbone amide linke
r (BAL) approach allows for the preparation of C-terminal-modified and cycl
ic peptides, small organic molecules, and modified amino sugars, as well as
combinatorial synthesis applications.