Bonding through phosphodiester moiety: Its implications in pharmaceutical modifications

Phosphodiester linkage is biologically essential with two ester moieties on single phosphoric acid. The ester linkage is formed by the reaction of carboxylic acid and alcohol. In the phosphodiester group, the carboxylic acid is replaced by phosphoric acid, and esterification occurs at two sites. Classically, the nomenclature of phosphodiester is generated for the phosphodiester linkages in nucleotides. The presence of a phosphodiester bond renders the stabilization of genetic material. Hydrolysis of phosphodiester bonds can either occur under enzymatic or alkaline conditions. However, the stability of phosphodiester bonds in deoxyribonucleotides is higher than in ribonucleotides. Phosphodiester bond is also present in biologically important cAMP, phospholipids, sphingomyelins, and glycerophospholipids. Usually, every biological molecule is activated by introducing a phosphate moiety. Many kinases are involved in maintaining normal human physiology. Phosphodiester kinase (phosphodiesterase) enzymes are present in the center stage of many physiological functions, and a review of phosphodiesterase inhibition is beyond the scope of this chapter. This chapter highlights the formation of phosphodiester bonds by chemical modification and its applications.