Large scale, liquid phase synthesis of oligonucleotides by the phosphoramidite approach

Abstract
A new method for the liquid phase synthesis of oligonucleotldes is described which makes use of polyethylene glycol (PEG) as soluble support and phosphoramldlte derivatives as synthons. The new synthetic protocol was applied to a quite large scale production (about 100 μtmoles) of such compounds up to the 20mer level. This solution method, called HELP High Efficiency Liquid Phase) Plus, appears effective in terms of speed and coupling yield and can be evaluated for the production of large amount of ollgonucleotldes.