Improved Utility of Photolabile Solid Phase Synthesis Supports for the Synthesis of Oligonucleotides Containing 3‘-Hydroxyl Termini

Abstract

Oligonucleotides are synthesized on, and cleaved from, a solid phase support (6) using the o-nitrobenzyl intramolecular photochemical redox reaction. The yields of isolated oligonucleotides relative to yields obtained using conventional hydrolytic cleavage vary between 67% and 82.5%. Synthesis of oligonucleotides using phosphoramidites that do not contain N-benzoyl protecting groups enables one to photolytically cleave the biopolymers in good yields using a commonly available UV irradiation source. Tritium labeling indicates that less than 3% thymidine.thymidine photodimers are formed during photolytic cleavage of polythymidylates from 6 using a transilluminator. No UV-induced damage is detected via HPLC analysis of enzymatically digested oligonucleotides that were obtained following photolytic cleavage from 6.