Inchemistry, aphosphodiester bond occurs when exactly two of thehydroxyl groups (−OH) inphosphoric acid react with hydroxyl groups on other molecules to form twoester bonds. The "bond" involves this linkageC−O−PO−2O−C.[1] Discussion of phosphodiesters is dominated by their prevalence inDNA andRNA, but phosphodiesters occur in other biomolecules, e.g.acyl carrier proteins,phospholipids and the cyclic forms of GMP and AMP (cGMP andcAMP).[2]
Phosphodiester bonds make up thebackbones ofDNA andRNA. In the phosphodiester bonds of nucleic acids, a phosphate is attached to the 5' carbon of one nucleoside and to the 3' carbon of the adjacent nucleoside. Specifically, it is the phosphodiester bonds that link the3' carbon atom of one sugar molecule and the 5' carbon atom of another (hence the name 3', 5' phosphodiester linkage used with reference to this kind of bond in DNA and RNA chains).[3] The involved saccharide groups aredeoxyribose in DNA andribose in RNA. In order for the phosphodiester bond to form, joining thenucleosides, the tri-phosphate or di-phosphate forms of the nucleotide building blocks are broken apart to give off energy required to drive theenzyme-catalyzed reaction.[4] In DNA replication, for example, formation of the phosphodiester bonds is catalyzed by aDNA polymeraseenzyme, using a pair ofmagnesiumcations and other supporting structures.[3] Formation of the bond occurs not only in DNA and RNA replication, but also in the repair and recombination of nucleic acids, and may require the involvement of various polymerases, primers, and/or ligases. During the replication of DNA, for example, theDNA polymerase I leaves behind a hole between the phosphates in the newly formed backbone.DNA ligase is able to form a phosphodiester bond between the nucleotides on each side of the gap.[2]
Phosphodiesters are negatively charged atpH 7.[5] The negative charge attractshistones, metal cations such asmagnesium, andpolyamines [needs citation]. Repulsion between these negative charges influences the conformation of the polynucleic acids.
Hydrolysis (breaking) of phosphodiester bonds can be promoted in several ways.Phosphodiesterases are enzymes that catalyze the hydrolysis of the phosphodiester bond. These enzymes are involved in repairing DNA and RNA sequences, nucleotide salvage, and in the conversion of cGMP and cAMP to GMP and AMP, respectively.[2] Hydrolysis of the phosphodiester bond also occurs chemically and spontaneously, without the aid of enzymes. For example, simpleribose (in RNA) has one morehydroxyl group thandeoxyribose (in DNA), making the former less stable and more susceptible toalkaline hydrolysis, wherein relatively high pH conditions induce the breaking of the phosphodiester linkage between tworibonucleotides. The relative instability of RNA under hydroxyl attack of its phosphodiester bonds makes it inadequate for the storage of genomic information, but contributes to its usefulness intranscription andtranslation.[2]