A phosphodiester bond is a group of strong covalent bonds between the phosphorus atom in a phosphate group and two other molecules over two ester bonds. Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of DNA. In DNA and RNA, the phosphodiester bond is the linkage between the 3' Carbon atom and the 5' Carbon of the ribose sugar.

The phosphate groups in the phosphodiester bond are very negatively charged. Because the phosphate groups are so negatively charged, there is a large repulsion which forces the phosphates to take opposite sides of the DNA strands.

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. When a single phosphate or two phosphates known as pyrophosphates break away and catalyze the reaction, the phosphodiester bond is formed.

Phosphodiester bonds can be catalyzed by the action of phosphodiesterases which play an important role in repairing DNA sequences.

In biological systems, the phosphodiester bond between two ribonucleotides can be broken by alkaline hydrolysis because of the free 2' hydroxyl group.

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.

See also

• Phosphodiesterase, Phosphodiesterase inhibitor
• DNA replication, DNA, ATP
• Teichoic acid, DNase I