Facile synthesis of oligonucleotides on solid support using pyridine derivatives for amino and phosphate protection

Abstract

The picolinoyl group has been used for amino protection in the case of all the three deoxynucleosides-dC, dA and dG, and good yields of N-protected nucleosides are obtained. This pyridine derivative along with another pyridine derivative, viz. (α-pyridyl) methyl, an autocatalytic phosphate protecting group, has been used successfully in the synthesis of two oligonucleotides, d(TACGTTTTGCT) and d(ACCGATATCGT) following solid phase methodology. The good yields of these 11-mers (48 and 45%, respectively) are attributed to the greater solubilising effect generated due to the combination of these two groups. The structures of these oligomers have been confirmed by enzymatic hydrolysis with snake venom phosphodiesterase followed by alkaline phosphatase.