Solid phase synthesis of oligonucleotides on a crosslinked polyacrylmorpholide support

Abstract

A suitable support for the synthesis of oligonucleotides by the phosphodi- and triester approaches was prepared by treatment of commercially available crosslinked polyacrylmorpholide beads with piperazine. The resulting polymer was used as a support for the synthesis of the self complementary decanucleotide d(T-C-G-G-A-T-C-C-G-A). An analog of dDMTrt in which one of the methoxy groups had been replaced by a carboxymethyloxy group was anchored to the polymer by an amide addition of an excess of protected nucleotide using phosphodiester methodology. Polymer supported synthesis by the phosphotriester approach of the octanucleotide d(T-T-T-T-T-T-T-T) and the hexanucleotide d(G-C-C-C-A-T) is also described. In this case 5'-O-dimethoxytritylthymidine 3'-O-monophthalate was synthesized and linked to the piperazinylated polymer. For the chain extension(3' to 5') a very simple deprotection and coupling cycle was devised.