Overview

Phosphodiester bond forms when a phosphoric acid molecule (H₃PO₄) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.

Phosphodiester Bonds Link Nucleotides Together

DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is composed of a nitrogenous base (adenine, guanine, thymine, cytosine, or uracil), a pentose sugar, and a phosphate molecule (PO₃⁻⁴). In a polynucleotide chain, nucleotides are linked together by phosphodiester bonds, where each phosphate group forms two ester bonds with its neighboring sugar molecules. The first ester bond already exists between the phosphate group and the 5' carbon of the pentose sugar of the nucleotide. The second ester bond is formed between the hydroxyl group (–OH) attached to the 3’ carbon of the preceding sugar molecule and the phosphate group. The formation of each ester bond removes one water molecule. A class of enzymes called polymerases tocatalyze, or accelerate, the formation of phosphodiester bonds.

Phosphodiester bonds in a polynucleotide chain form an alternating pattern of sugar and phosphate residues called the sugar-phosphate backbone. Phosphodiester bonds impart directionality to a polynucleotide chain. The polynucleotide chain has a free 5' phosphate group at one end and a free 3' hydroxyl group at the other. These ends are called the 5' end and the 3' end, respectively. The directionality of nucleic acids is essential for DNA replication and RNA synthesis.