phosphodiesters

Phosphodiesters are diesters of phosphoric acid, in which the phosphorus atom is bound by two ester linkages to two alcohol groups. In biochemistry, the term is most often applied to the phosphodiester bonds that form the backbone of nucleic acids.

In DNA and RNA, each phosphodiester bond links the 3' hydroxyl of one sugar (deoxyribose or ribose) to the 5' hydroxyl of the next sugar through a phosphate group, creating a sugar–phosphate–sugar chain. The repeating linkages give the nucleic acid a negatively charged backbone at physiological pH, which influences its structure, stability, and interactions with proteins and ions. The chain has directionality, running from the 5' end to the 3' end.

Formation and cleavage of phosphodiester bonds are central to nucleic acid metabolism. They are formed by condensation reactions during DNA replication and RNA transcription, catalyzed by polymerases, with the release of water. They are cleaved by nucleases and, under certain conditions, by hydrolysis. Alkaline conditions preferentially promote phosphodiester cleavage; RNA is more prone to hydrolysis than DNA because of the 2' hydroxyl group on ribose.

Beyond nucleic acids, phosphodiesters occur in other biomolecules, such as certain phospholipid head groups where a phosphate is linked to two moieties via phosphodiester bonds. In chemistry, “phosphodiester” also denotes any diester of phosphoric acid formed with two alcohol groups, a broader structural class beyond biological backbones.