Protocols for Oligonucleotides and Analogs

Volume 20 of the series Methods in Molecular Biology pp 465-496

Solid-Phase Supports for Oligonucleotide Synthesis

  • Richard T. PonAffiliated withDepartment of Medical Biochemistry, University of Calgary

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The solid-phase strategy for oligonucleotide synthesis has been responsible for much of the widespread utilization of synthetic oligonucleotides. Indeed, without this approach, the chemical synthesis of oligonucleotides would have remained a difficult and tedious task suitable for only the most dedicated chemist. Now of course, as anyone owning an automated synthesizer knows, the solid-phase synthesis of oligonucleotides is as easy as pressing a few buttons. However, despite the obvious advantages of solid-phase synthesis, the development of satisfactory procedures for oligonucleotide synthesis required almost 20 years from the first introduction of this technique. This was primarily because of two obstacles that had to be overcome. The first was the need for rapid and highly efficient coupling reactions, and the second was the need for a suitable solid-phase support. This chapter is devoted to a treatment of the solid-phase supports and the important covalent linkage that binds the oligonucleotide to it.