AN OPTIMIZED POLYSTYRENE SUPPORT FOR RAPID, EFFICIENT OLIGONUCLEOTIDE SYNTHESIS

An optimized type of polystyrene has been developed as a solid support for automated oligonucleotide synthesis. The non-swelling, rigid beads possess the attractive features of rapid reaction kinetics, efficient washing with organic solvents, and mechanical stability. Pore size, particle size, and polymerization formula and conditions have been optimized. The support material is derivatized to give primary amino functionality, which is near quantitatively coupled to 3' p-nitrophenyl succinate nucleosides. Loading of the nucleosides can be precisely controlled in a range of 5 to 70-mu-mole per gram. The high yield synthesis of oligonucleotides, by phosphoramidite chemistry has been demonstrated up to 120 bases in length. Side reactions, such as extraneous chain growth, are minimized due to the lack of reactive functionality on the new support surface.