Phosphodiester Bond

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 central 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 pK_a 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.

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

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.

Phosphodiester bonds are also found in O-phosphonolipids (phospholipids).