2'-3'-Dideoxyguanosine-5'-triphosphate
[CAS# 68726-28-3]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism >> Transferase inhibitor
• Name: 2'-3'-Dideoxyguanosine-5'-triphosphate
• Synonyms: ddGTP; [[(2S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• Protein Sequence: N
• Molecular Formula: C₁₀H₁₆N₅O₁₂P₃
• Molecular Weight: 491.18
• CAS Registry Number: 68726-28-3
• SMILES: C1C[C@@H](O[C@@H]1COP(=O)(O)OP(=O)(O)OP(=O)(O)O)N2C=NC3=C2N=C(NC3=O)N

Properties

• Solubility: wate 5 mg/mL (Expl.)

Discovory and Applicatios

2',3'-Dideoxyguanosine 5'-triphosphate (commonly abbreviated as ddGTP) is a synthetic nucleotide analog structurally similar to the natural guanosine triphosphate (GTP), but lacking hydroxyl groups at the 2' and 3' positions of the ribose sugar. This structural alteration prevents the formation of the 3'-5' phosphodiester bond necessary for DNA chain elongation, making ddGTP a chain terminator when incorporated by DNA polymerases during DNA synthesis.

The compound is the triphosphorylated form of 2',3'-dideoxyguanosine (ddG), a nucleoside analog designed to interfere with nucleic acid synthesis. The absence of the 3'-hydroxyl group in ddGTP means that once it is incorporated into a growing DNA strand, further addition of nucleotides is blocked, effectively terminating DNA chain extension. This property has made ddGTP a vital reagent in molecular biology, particularly in DNA sequencing and enzymatic studies.

The development of ddGTP is linked to the broader class of dideoxynucleotides, which were first applied in the Sanger method of DNA sequencing. In this method, ddGTP is used alongside the natural deoxynucleotides to randomly terminate DNA synthesis at guanine residues. By labeling the DNA fragments generated through incorporation of ddGTP and other dideoxynucleotides, researchers can determine the DNA sequence through electrophoretic separation. The high specificity and efficiency of ddGTP in terminating DNA synthesis have made it indispensable for genetic analysis and genome sequencing.

Synthetically, ddGTP is produced by phosphorylation of ddG through multi-step chemical or enzymatic processes. The compound’s stability and purity are crucial for its use in sequencing reactions and polymerase assays. Commercially available ddGTP is widely utilized in research laboratories for DNA sequencing and polymerase chain reaction (PCR)-based applications requiring chain termination.

Beyond sequencing, ddGTP serves as a tool to investigate DNA polymerase activity and fidelity. Studies involving ddGTP incorporation provide insight into enzyme substrate preferences, mechanisms of nucleotide addition, and polymerase inhibition. It is also employed in assays designed to screen for polymerase inhibitors and to characterize DNA synthesis pathways.

While ddGTP itself is not used as a therapeutic agent, its mechanism of chain termination is foundational to the design of antiviral drugs targeting viral polymerases, especially in the treatment of retroviral infections. Analogous compounds structurally related to ddGTP have been developed as nucleoside reverse transcriptase inhibitors (NRTIs), which inhibit viral DNA replication by causing premature chain termination.

In summary, 2',3'-dideoxyguanosine 5'-triphosphate is a chemically modified nucleotide analog widely used as a DNA chain terminator in molecular biology. Its role in the Sanger sequencing method has been crucial for the advancement of genetic research. Additionally, ddGTP is an important biochemical tool for studying DNA polymerase function and nucleic acid metabolism. Although not a drug itself, ddGTP’s properties have influenced the development of antiviral therapies based on chain termination.

References

1984. Stability of tubulin polymers formed with dideoxyguanosine nucleotides in the presence and absence of microtubule-associated proteins. The Journal of biological chemistry, 259(4).
DOI: 10.1016/s0021-9258(17)43381-3

2001. Crystal structures of a ddATP-, ddTTP-, ddCTP, and ddGTP- trapped ternary complex of Klentaq1: Insights into nucleotide incorporation and selectivity. Protein science: a publication of the Protein Society, 10(6).
DOI: 10.1110/ps.250101

2011. Structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis. Proceedings of the National Academy of Sciences of the United States of America, 108(43).
DOI: 10.1073/pnas.1114496108