dideoxynucleoside

A dideoxynucleoside is a type of nucleoside analog that lacks a hydroxyl group at the 3' position of its sugar ring. This structural modification is critical because it prevents the formation of a phosphodiester bond during DNA synthesis. In natural DNA replication, a new nucleotide is added to the growing chain by forming a phosphodiester bond between the 3' hydroxyl group of the last nucleotide and the 5' phosphate group of the incoming nucleotide.

When a dideoxynucleoside is incorporated into a growing DNA strand, it terminates further elongation. This is because, lacking the 3' hydroxyl group, no subsequent nucleotide can be added. This property is fundamental to the dideoxy chain-termination method of DNA sequencing, also known as the Sanger sequencing method. In this technique, small amounts of dideoxynucleotides are added to a DNA replication reaction. When a dideoxynucleotide is randomly incorporated, it prematurely stops the synthesis of that particular DNA strand. By using different dideoxynucleotides labeled with distinct fluorescent markers, scientists can determine the sequence of bases in a DNA molecule.

Dideoxynucleosides also have significant therapeutic applications, particularly as antiviral drugs. Many drugs used to treat viral infections, such as HIV, are dideoxynucleoside reverse transcriptase inhibitors (NRTIs). These drugs mimic natural nucleosides and are incorporated into the viral DNA by the viral reverse transcriptase enzyme. Once incorporated, they terminate the DNA chain, thus inhibiting viral replication. Examples include zidovudine (AZT) and lamivudine.