Solid-Phase Synthesis of Circular Oligonucleotides

A protocol for the straightforward preparation of small circular oligodeoxyribonucleotides (2–28 nt) is reported. The assembly of the oligonucleotide chain (standard phosphoramidite chemistry) and cyclization by the phosphotriester method take place on a tailor-made nucleotide-derivatized solid support. Although cyclization yields are moderate, the procedure exploits a synthesis design that allows selective cleavage of the circular oligonucleotide from the support, which facilitates isolation of the target molecule by simple filtration.