Abstract

Solid-phase synthesis is typically performed on linkers attached to various solid supports (or resins). A number of different solid supports, ranging from membranes to photolithographic chips to polyethylene pins, have been used for combinatorial synthesis. Choosing the correct linker is a crucial step for combinatorial synthesis on solid support. The linker must be compatible with all the synthetic steps, yet labile under cleavage conditions that do not cause decomposition of the compounds generated in the library. Many of the linkers commonly used for combinatorial synthesis are borrowed from previous research on the solid-phase synthesis of peptides. The appropriate linker is often dictated by the functionality present in the specific class of molecules of interest. This chapter provides a description of the strengths and limitations of various linkers, with a particular emphasis on linkers that are appropriate for combinatorial synthesis. Additional details, particularly regarding the commercially available linkers is provided in the synthetic notes of catalogs for purchasing resins for solid-phase peptide or combinatorial synthesis.

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