2',3'-Dideoxyguanosine
[CAS# 85326-06-3]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Deoxynucleotides and their analogues
• Name: 2',3'-Dideoxyguanosine
• Synonyms: 2-Amino-9-[5-(hydroxymethyl)oxolan-2-yl]-3H-purin-6-one
• Protein Sequence: N
• Molecular Formula: C₁₀H₁₃N₅O₃
• Molecular Weight: 251.24
• CAS Registry Number: 85326-06-3
• SMILES: C1C[C@@H](O[C@@H]1CO)N2C=NC3=C2N=C(NC3=O)N

Properties

• Density: 1.9±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.863, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P280-P301+P312-P302+P352-P305+P351+P338

Discovory and Applicatios

2',3'-Dideoxyguanosine is a modified nucleoside analogue that plays a significant role in molecular biology and the field of antiviral therapy. It is a synthetic derivative of guanosine, where both the 2'- and 3'-hydroxyl groups of the sugar moiety are replaced by hydrogen atoms. This modification prevents the elongation of the nucleic acid chain, making it an important tool for inhibiting viral replication, particularly in the treatment of HIV (Human Immunodeficiency Virus) infections.

The discovery of 2',3'-dideoxyguanosine occurred in the 1980s during the search for antiviral agents capable of targeting retroviruses, particularly HIV. As part of a class of compounds known as dideoxynucleosides, 2',3'-dideoxyguanosine was found to act as an effective chain terminator during the reverse transcription process of viral RNA into DNA. By inhibiting the reverse transcriptase enzyme, which is responsible for catalyzing this process, 2',3'-dideoxyguanosine prevents the synthesis of viral DNA, thereby reducing viral replication in infected cells.

In clinical applications, 2',3'-dideoxyguanosine, also known as ddG, is used in the treatment of HIV infections. It is part of a broader group of nucleoside reverse transcriptase inhibitors (NRTIs), which are commonly included in combination antiretroviral therapy (cART). These therapies aim to reduce the viral load of HIV in patients and prevent the progression to Acquired Immunodeficiency Syndrome (AIDS). ddG has demonstrated efficacy in inhibiting the HIV virus, particularly in cases where resistance to other NRTIs has developed. However, due to its toxicity and side effects, such as mitochondrial toxicity, 2',3'-dideoxyguanosine is not as widely used today as some of the newer NRTIs, like tenofovir or lamivudine.

The compound’s primary mechanism of action is its incorporation into the growing viral DNA strand during reverse transcription. Once incorporated, 2',3'-dideoxyguanosine lacks the necessary 3'-hydroxyl group required for the formation of the next phosphodiester bond, thus terminating the chain and preventing further DNA synthesis. This mechanism is shared with other dideoxynucleosides, such as 2',3'-dideoxyadenosine (ddA) and 2',3'-dideoxycytidine (ddC), but the specific antiviral activity depends on the viral strain and the drug's pharmacokinetics.

In addition to its use in antiviral therapy, 2',3'-dideoxyguanosine is also employed as a research tool in molecular biology. It is used in studies that aim to understand the mechanisms of reverse transcription and viral replication. The compound’s ability to terminate DNA chain elongation has made it a valuable reagent in experiments that involve DNA sequencing or the construction of specific DNA libraries. Researchers can use ddG to selectively halt DNA polymerization in vitro, allowing them to study the properties of the DNA sequence up to the point of termination.

While 2',3'-dideoxyguanosine has proven effective in the laboratory and in clinical settings, it is not without its challenges. The compound has been associated with a range of toxic side effects, particularly when used in high doses or over extended periods. These side effects include peripheral neuropathy, lactic acidosis, and mitochondrial dysfunction, all of which limit its clinical use. Consequently, it is typically prescribed only when other treatment options are not viable, or when the virus has developed resistance to other drugs in the same class.

In summary, 2',3'-dideoxyguanosine is a key nucleoside analogue used primarily in the treatment of HIV infections as part of antiretroviral therapy. Its ability to inhibit viral replication by acting as a chain terminator during reverse transcription makes it an important therapeutic agent. While it has been largely replaced by newer and less toxic NRTIs, it continues to have value as a research tool in molecular biology and virology. The development of 2',3'-dideoxyguanosine marked a significant advancement in antiviral drug discovery and provided a foundation for subsequent innovations in the treatment of retroviral infections.