2',3'-Dideoxyadenosine triphosphate
[CAS# 24027-80-3]

Identification

• Classification: Biochemical >> Inhibitor >> Transmembrane transporters >> Potassium channel inhibitor
• Name: 2',3'-Dideoxyadenosine triphosphate
• Synonyms: [[(2S,5R)-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• Protein Sequence: N
• Molecular Formula: C₁₀H₁₆N₅O₁₁P₃
• Molecular Weight: 475.18
• CAS Registry Number: 24027-80-3
• SMILES: C1C[C@@H](O[C@@H]1COP(=O)(O)OP(=O)(O)OP(=O)(O)O)N2C=NC3=C(N=CN=C32)N

Properties

• Density: 2.4±0.1 g/cm³ Calc.^*
• Boiling point: 843.5±75.0 ºC 760 mmHg (Calc.)^*
• Flash point: 463.9±37.1 ºC (Calc.)^*
• Index of refraction: 1.846 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Discovory and Applicatios

2',3'-Dideoxyadenosine triphosphate (ddATP) is a nucleotide analog of adenosine triphosphate (ATP) characterized by the absence of hydroxyl groups at the 2' and 3' positions of its ribose sugar. This structural modification prevents the formation of phosphodiester bonds during nucleic acid synthesis, causing chain termination when incorporated into DNA. The discovery and application of ddATP are closely tied to its role as a critical tool in DNA sequencing and molecular biology research.

The development of ddATP arose from efforts to improve methods for DNA sequencing. In the 1970s, Frederick Sanger and colleagues introduced the chain termination method, also known as Sanger sequencing, which revolutionized genetic analysis. ddATP, along with other dideoxynucleotides (ddNTPs), was central to this technique. By incorporating ddATP into a growing DNA strand during replication, the DNA polymerase is unable to add further nucleotides, effectively terminating synthesis at specific adenine bases. This termination generates DNA fragments of varying lengths that can be separated and analyzed to deduce the DNA sequence.

In its triphosphate form, ddATP serves as a substrate for DNA polymerases in vitro. Its lack of a 3' hydroxyl group means that once incorporated, it prevents elongation of the DNA strand. This property enables precise determination of nucleotide sequences when used in combination with the other three ddNTPs during the sequencing reaction. The chain termination method using ddATP facilitated the sequencing of entire genomes and remains foundational to many sequencing technologies, although newer high-throughput methods have since emerged.

Beyond sequencing, ddATP is also used as a biochemical tool to study DNA polymerase activity and fidelity. Its ability to act as a terminator helps researchers understand enzyme mechanisms and the effects of various mutations on DNA replication. Furthermore, ddATP analogs have been explored in antiviral therapies, especially targeting viral reverse transcriptases in diseases such as HIV. By causing premature termination of viral DNA synthesis, these analogs inhibit viral replication.

The chemical synthesis of ddATP involves protection and selective modification of the ribose sugar to remove the 2' and 3' hydroxyl groups, followed by phosphorylation to introduce the triphosphate moiety. The compound must be handled with care in laboratory settings due to its potent biological activity.

Overall, 2',3'-dideoxyadenosine triphosphate is a pivotal molecule in molecular biology, contributing significantly to the advancement of genetic sequencing and enzymology. Its unique structural features enable precise control over DNA synthesis, making it invaluable for research and diagnostic applications. The continued use and study of ddATP underscore its importance in understanding nucleic acid biology and developing therapeutic strategies.

References

1975. 3�-Deoxyadenosine and Other Polynucleotide Chain Terminators. Antineoplastic and Immunosuppressive Agents.
DOI: 10.1007/978-3-642-65806-8_37

2010. Replication through an abasic DNA lesion: structural basis for adenine selectivity. The EMBO Journal, 29(10).
DOI: 10.1038/emboj.2010.64

2011. Learning from Directed Evolution: Thermus aquaticus DNA Polymerase Mutants with Translesion Synthesis Activity. Chembiochem: a European journal of chemical biology, 12(7).
DOI: 10.1002/cbic.201000783