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A phosphodiester bond is a group of strong covalent bonds between a phosphate group and two 5-carbon ring carbohydrates (pentoses) over two ester bonds. Phosphodiester bonds are essential to all known life, as they make up the backbone of each helical strand of DNA. In DNA and RNA, the phosphodiester bond is the linkage between the 3' carbon atom of one sugar molecule and the 5' carbon atom of another; the sugar molecules being deoxyribose in DNA and ribose in RNA.
The phosphate groups in the phosphodiester bond are negatively charged. Because the phosphate groups have a pKa near 0, they are negatively charged at pH 7. This repulsion forces the phosphates to take opposite sides of the DNA strands and is neutralized by proteins (histones), metal ions such as magnesium, and polyamines.
In order for the phosphodiester bond to be formed and the nucleotides to be joined, the tri-phosphate or di-phosphate forms of the nucleotide building-blocks are broken apart to give off energy required to drive the enzyme-catalyzed reaction.
In biological systems, phosphodiester bonds joining the pentose groups of ribonucleic acids can be broken through alkaline hydrolysis, in which the 2' hydroxyl group acts as a nucleophile in this intramolecular displacement, producing a 2',3'-cyclic monophosphate derivative that, upon further hydrolysis, yields a mixture of 2'- and 3'-monophosphates. Deoxyribonucleic acids, lacking a 2'-OH, are stable under similar (basic) conditions.
Enzyme activity 
A phosphodiesterase is an enzyme that catalyzes the hydrolysis of phosphodiester bonds, for instance a bond in a molecule of cyclic AMP or cyclic GMP.
An enzyme that plays an important role in the repair of oxidative DNA damage is the 3'-phosphodiesterase.
During the replication of DNA, there is a hole between the phosphates in the backbone left by DNA polymerase I. DNA ligase is able to form a phosphodiester bond between the nucleotides.
During transcription of DNA, RNA polymerase catalyze the formation of the phosphodiester bonds that link the ribonucleotides together and form the sugar-phosphate backbone of the RNA chain.
- "Nomenclature of Lipids - Phospholipids". IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Retrieved 22 October 2011.
- Bruce Albert et al. - Essential Cell Biology p. 235
Bruce Albert et al. - Essential Cell Biology 3rd ed., Garland Science 2009
See also 
- Phosphodiesterase inhibitor
- DNA replication, DNA, ATP
- Teichoic acid, DNase I
- Nick (DNA)