Modern methods of nucleic acid synthesis on polymeric supports

Abstract

Abstract Deoxyoligonucleotides can be synthesized rapidly and in high yield because of recent advances in nucleic acid chemistry. Key innovations include solid phase synthesis of silica-based support and the development of stable deoxynucleoside phosphoramidites as synthons. When incorporated into manual, semiautomatic, or automatic instruments, these new procedures can be used to prepare probes, mixed probes, deoxyoligonucleotides for priming DNA synthesis, analogues of deoxyoligonucleotides, and genes. Oligoribonucleotides have also been prepared. The most successful approach so far developed involves using 2′-protected nucleosides as synthons and bis(diisopropylamino)methoxyphosphine as a phosphitylating reagent. A regioselective condensation route leading to the exclusive synthesis of 3′–5′ internucleotide linkages is possible.