2'-Deoxy-2'-fluoroguanosine
[CAS# 78842-13-4]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Deoxynucleotides and their analogues
• Name: 2'-Deoxy-2'-fluoroguanosine
• Synonyms: 2'-FdG
• Molecular Formula: C₁₀H₁₂FN₅O₄
• Molecular Weight: 285.23
• Protein Sequence: N
• CAS Registry Number: 78842-13-4
• SMILES: C1=NC2=C(N1[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)F)N=C(NC2=O)N

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

2'-Deoxy-2'-fluoroguanosine is a modified nucleoside that has attracted much attention in the field of medicinal chemistry. This compound features a fluorine atom substituted at the 2' position of the deoxyribose sugar, which has unique properties that enhance its stability and functionality. The discovery and application of 2'-deoxy-2'-fluoroguanosine has opened new avenues for antiviral therapy, cancer treatment, and biochemical research.

The discovery of 2'-deoxy-2'-fluoroguanosine stems from the development of nucleoside analogs with improved therapeutic properties. Researchers aim to create nucleosides that can better resist enzymatic degradation while maintaining or enhancing biological activity. The introduction of a fluorine atom at the 2' position is a strategic modification because the small size and high electronegativity of fluorine contribute to improved stability and altered biochemical interactions. This modification was first reported in the second half of the 20th century and marked a major advance in the design of nucleoside analogs.

2'-Deoxy-2'-fluoroguanosine has shown promise as an antiviral agent. Its incorporation into viral DNA can cause chain termination or induce mutations that inhibit viral replication. This mechanism makes it a potential candidate for the treatment of various viral infections, including those caused by herpes viruses and hepatitis B. The enhanced stability of this compound allows for more effective inhibition of viral activity, making it a valuable addition to the development of antiviral drugs.

In oncology, 2'-deoxy-2'-fluoroguanosine is being explored for its potential as a chemotherapeutic agent. Cancer cells, characterized by rapid division and high metabolic activity, are particularly susceptible to nucleoside analogs that disrupt DNA synthesis. Incorporation of 2'-deoxy-2'-fluoroguanosine into the DNA of cancer cells interferes with the replication process, leading to cell death. This property makes it a candidate for the treatment of certain types of cancer, such as hematological malignancies and solid tumors.

The stability and unique properties of 2'-deoxy-2'-fluoroguanosine make it a valuable tool in biochemical research. It is used to study DNA synthesis and repair mechanisms, providing insights into fundamental cellular processes. Researchers use this compound to study the effects of nucleoside modifications on DNA structure and function, thereby deepening our understanding of gene regulation and expression.

Because 2'-deoxy-2'-fluoroguanosine is resistant to enzymatic degradation, it is used in pharmacokinetic studies to evaluate the absorption, distribution, metabolism, and excretion (ADME) of nucleoside analogs. These studies are essential for designing nucleoside drugs with improved bioavailability and therapeutic properties, thereby providing more effective treatments for various diseases.

References

1994. Inhibition of influenza virus transcription by 2'-deoxy-2'-fluoroguanosine. Antimicrobial Agents and Chemotherapy, 39(11).
DOI: 10.1128/aac.39.11.2454

1999. Chemical and Enzymatic Synthesis and Antiviral Properties of 2′-Deoxy-2′-fluoroguanosine. Nucleosides and Nucleotides, 18(4-5).
DOI: 10.1080/15257779908041541

2023. The Effects of FANA Modifications on Non-canonical Nucleic Acid Structures. Handbook of Chemical Biology of Nucleic Acids.
DOI: 10.1007/978-981-19-9776-1_16