Microwave-Dependent Thermo-Release Approach for Oligonucleotides 5′-Phosphorylation

A method for phosphorylating oligonucleotides using a thermosensitive “trigger” is hereby presented. The recovery of the phosphate specifically takes place under neutral conditions when subjected to an elevated temperature. Two identical thermolabile protecting groups are differentially removed with the initial release occurring swiftly and the second at a more gradual pace. The delayed deprotection of the second group led to the development of a method for the purification of 5′-phosphorylated oligonucleotides. Microwave irradiation enables the rapid attainment of complete deprotection, in contrast to conventional heating methods.