Dideoxyguanine

Dideoxyguanine, also known as ddG or 2',3'-dideoxyguanosine, is a synthetic nucleoside analog. It is structurally similar to the natural deoxyguanosine, a component of DNA, but with a key difference: it lacks hydroxyl groups at both the 2' and 3' positions of the deoxyribose sugar. This absence of the 3'-hydroxyl group is crucial to its biological activity.

When dideoxyguanine is incorporated into a growing DNA chain by a DNA polymerase, it acts as a chain terminator. Because there is no 3'-hydroxyl group available to form a phosphodiester bond with the next incoming nucleotide, DNA synthesis halts at that point. This property has made dideoxyguanine and its derivatives important tools in molecular biology, particularly in DNA sequencing techniques like the Sanger sequencing method. In this method, dideoxynucleotides are used to generate DNA fragments of varying lengths, which can then be separated and analyzed to determine the precise order of nucleotides in a DNA molecule.

Dideoxyguanine itself has limited direct therapeutic applications. However, its mechanism of action as a chain terminator has inspired the development of antiviral drugs. For instance, some drugs used to treat HIV infection are dideoxynucleoside reverse transcriptase inhibitors, which function by incorporating into the viral DNA and halting its replication. While dideoxyguanine is not directly used as such a drug, its chemical modification into compounds like didanosine (2',3'-dideoxyinosine), which is then metabolized to a dideoxyguanine triphosphate analog, highlights the importance of this structural motif in medicinal chemistry.