5-Aminouridine
[CAS# 2149-76-0]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antifungal drugs
• Name: 5-Aminouridine
• Synonyms: 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• Molecular Formula: C₉H₁₃N₃O₆
• Molecular Weight: 259.22
• CAS Registry Number: 2149-76-0
• SMILES: C1=C(C(=O)NC(=O)N1[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O)N

Properties

• Density: 1.7±0.1 g/cm³ Calc.^*
• Index of refraction: 1.666 (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

5-Aminouridine is a modified nucleoside that has attracted attention in biochemical and medicinal research due to its unique structural characteristics and potential biological functions. It is derived from uridine, one of the four standard nucleosides in RNA, through the substitution of an amino group at the 5-position of the uracil ring. This substitution results in altered hydrogen bonding and electronic properties, distinguishing 5-aminouridine from its parent compound in terms of chemical reactivity and biological interactions.

The discovery of 5-aminouridine dates back to the mid-20th century, during investigations into the chemical modification of nucleosides and their incorporation into nucleic acids. Researchers synthesized 5-substituted uridine analogs to explore their base-pairing properties, enzymatic recognition, and metabolic stability. The amino substitution at the 5-position was of particular interest because it influenced the tautomeric equilibrium of the base and potentially modified the base-pairing preferences within RNA. Early synthetic routes to 5-aminouridine involved diazotization and subsequent substitution reactions starting from uridine derivatives, yielding the target compound under controlled chemical conditions.

In terms of its biological activity, 5-aminouridine has been explored primarily as a research tool rather than as a therapeutic agent. Its incorporation into RNA sequences can be used to study structural and functional aspects of nucleic acids, including RNA folding, hybridization, and stability. The presence of the amino group can enhance hydrogen bonding capabilities, potentially altering the thermodynamic behavior of RNA duplexes or RNA-protein interactions. In molecular biology, such analogs are valuable in probing the effects of base modification on RNA structure and function.

Another area of interest in the application of 5-aminouridine has been its role in synthetic biology and nucleic acid therapeutics. Modified nucleosides like 5-aminouridine are used to develop synthetic oligonucleotides with improved properties for diagnostics or gene modulation. For example, incorporation of modified bases can enhance binding affinity, resistance to nuclease degradation, or specificity of antisense oligonucleotides and small interfering RNAs. Although 5-aminouridine is not commonly used in current therapeutic oligonucleotides, its chemical structure provides a model for designing other nucleoside analogs with improved pharmaceutical properties.

In addition, studies on 5-aminouridine have contributed to understanding nucleoside metabolism. The compound is recognized and processed by various enzymes involved in nucleoside salvage pathways, including nucleoside kinases and phosphorylases. Its metabolic fate and enzymatic handling provide insights into the substrate specificity and adaptability of these enzymes. By comparing the enzymatic activity on modified versus natural nucleosides, researchers have deepened their knowledge of how nucleoside metabolism can be harnessed or manipulated for therapeutic purposes.

5-Aminouridine has also been investigated in the context of mutagenesis and chemical carcinogenesis. Modified nucleosides can serve as analogs that mimic naturally occurring lesions or mutagenic bases. Incorporation of 5-aminouridine into DNA or RNA during replication or transcription may affect base-pairing fidelity, leading to misincorporation events or altered gene expression. This makes it useful in experimental models that explore the mechanisms of mutation and repair, as well as the role of nucleoside modifications in genetic stability.

Overall, 5-aminouridine is an example of how minor structural changes to nucleosides can significantly affect their chemical and biological properties. While it does not have widespread pharmaceutical application on its own, its study has expanded our understanding of nucleic acid chemistry and supported the development of new tools for biochemical research and synthetic biology.

References

1960. Nucleosides. XXVIII. Synthesis of Some 5-Substituted Uracils and Related Nucleosides. Journal of the American Chemical Society, 82(7).
DOI: 10.1021/ja01492a051

1975. Showdomycin, 5-Hydroxyuridine, and 5-Aminouridine. Antineoplastic and Immunosuppressive Agents.
DOI: 10.1007/978-3-642-65806-8_17

2015. Synthesis, reactivity, and biological activity of 5-aminouracil and its derivatives. Molecular Diversity, 19(2).
DOI: 10.1007/s11030-015-9595-1