Automation of the Liquid-Phase Synthesis of Biopolymers

The liquid-phase synthesis of biopolymers is an alternative to the solid-phase methodologies that are widely applied in spite of limitations in the use of heterogeneous media. The advantages of the liquid-phase approach are due to the fact that the support is alternatively soluble in the solvents used for the chemical reactions and insoluble in the mixtures used for the purification steps. Thus, the advantages of both 'solution' and 'solid-phase' methodologies can be properly integrated. At present the liquid-phase procedure, unlike solid-phase methods that have been highly automated, can be carried out only manually due to technical difficulties imposed by the cyclic repetition of dissolution and precipitation steps. The original apparatus proposed here performs, for the first time, all the steps required by the liquid-phase approach in a fully automatic way controlled by a user-friendly dedicated software. The automated liquid-phase methodology has been tested by synthesizing some sample oligonucleotides and the preliminary results are discussed in the present paper.