Abstract

The main issue associated with scalability of the oligonucleotide synthesis is the use of various apparatuses, methods, reagents and supports depending on scale. Supports based on polystyrene (PS) core, which are used in a large-scale mode, are not suitable for small scale synthesizers driven by gas pressure due to swelling and increasing back pressure. On the contrary, CPG (controlled pore glass) based supports have insufficient loadings to be considered for large-scale synthesis. To bridge the loading gap and remove the problem of swelling, our research focused on development of supports based on a solid core (CPG and other solid materials) bonded with a polymer layer that provides an excessively developed surface area and binding sites for succinic linkers. A solid core should prevent clogging small-scale synthesizers by limited swelling in organic solvents, and polymer coating should provide enhanced surface area, and consequently more space for heavier loadings.Several synthetic polymers were tested to develop hybrid supports, and small-scale solid phase synthesis was performed. The measured amount of crude oligonucleotides was often higher than for commercially available CPG control, and RP-HPLC analysis of the synthesised oligonucleotides showed high quality of the obtained material, comparable to commercially available CPG control.However, further study seems to be necessary to better understand alterations in structure of utilised polymers during the consequent steps of solid phase oligonucleotides synthesis. Also minor improvements in hybrid support composition need to be fulfilled in terms of final loadings to obtain commercially valuable product.