Chemical Syntheses of 3′ and 5′ Phosphorylated Oligonucleotides: An Overview

Oligonucleotides (ON) with a phosphate monoester group at their 3′ or 5′ end have applications in many fields. Initially, the reagents used for their synthesis were similar to those used for the introduction of internucleotidic phosphates. However, as nucleic acid chemistry evolved, demanding specifications (RNA compatibility, purification aid, simplicity of the deprotection reaction) led to the development of more and more sophisticated reagents. This review will present the evolution and the most recent methods of 3 ′ or 5 ′ terminal phosphorylation of oligonucleotides. It will also recall the criteria to be met in the quest for the ideal reagent.