N-Acetyl-2'-O-methylcytidine
[CAS# 113886-71-8]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Nucleoside intermediate
• Name: N-Acetyl-2'-O-methylcytidine
• Synonyms: N4-Acetyl-2'-O-methylcytidine
• Molecular Formula: C₁₂H₁₇N₃O₆
• Molecular Weight: 299.28
• CAS Registry Number: 113886-71-8
• SMILES: CC(=O)NC1=NC(=O)N(C=C1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)OC

Properties

• Solubility: Slightly soluble (6.6 g/L) (25 °C), Calc.^*
• Density: 1.58±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2016 ACD/Labs)

Safety Data

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

Discovery and Applications

N-acetyl-2'-O-methylcytidine is a chemically modified nucleoside characterized by an acetyl group at the N position of the ribose sugar and a methyl group at the 2' position. These modifications enhance its stability and functionality, making it valuable for applications in nucleic acid research and therapeutic development.

The discovery of N-acetyl-2'-O-methylcytidine stems from efforts to improve the chemical and enzymatic stability of nucleosides. Researchers aimed to modify the ribose and nucleobases to increase resistance to degradation and improve binding affinity. The acetyl group at the N position provides protection and increases hydrophobicity, while the 2'-O-methyl modification improves resistance to ribonucleases. These combined modifications produce a nucleoside with enhanced stability and functionality that can be used in a variety of applications.

N-acetyl-2'-O-methylcytidine is incorporated into nucleic acids, where the 2'-O-methyl modification protects the nucleoside from enzymatic degradation by ribonucleases. The acetyl group further stabilizes the molecule and can influence its interactions with other nucleic acids and proteins. These modifications make N-acetyl-2'-O-methylcytidine particularly useful in applications that require stable and functional nucleic acid molecules.

N-acetyl-2'-O-methylcytidine is used in the development of RNA therapeutics, including small interfering RNA (siRNA) and antisense oligonucleotides. The 2'-O-methyl modification increases the stability of these molecules, prolonging their activity in vivo and enhancing their therapeutic potential. This makes them more effective in gene silencing and regulation of gene expression, which can be used to treat a variety of diseases.

In oligonucleotide synthesis, N-acetyl-2'-O-methylcytidine is used to generate RNA sequences with enhanced stability and resistance to degradation. This is essential for creating reliable and durable nucleic acid-based tools for research and therapeutic applications.

N-acetyl-2'-O-methylcytidine is valuable in molecular biology research and can be used to study RNA structure and function. Its enhanced stability allows researchers to study RNA interactions and mechanisms in greater detail, advancing the understanding of genetic regulation and the development of RNA-based technologies.

The main advantages of N-acetyl-2'-O-methylcytidine are its enhanced stability and functionality. The 2'-O-methyl modification resists ribonuclease degradation, while the acetyl group further increases stability and influences molecular interactions. These properties make it an indispensable tool in research and therapeutic settings.

Despite the many advantages of N-acetyl-2'-O-methylcytidine, its use also presents challenges. The synthesis of modified nucleosides can be complex and costly. Furthermore, while modifications can improve stability, they can also affect the bioactivity and delivery of RNA therapeutics, requiring careful design and optimization for therapeutic applications.

References

2024. Recent advances in the potential role of RNA N4-acetylcytidine in cancer progression. Cell communication and signaling: CCS.
DOI: 10.1186/s12964-023-01417-5

2018. Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biology.
DOI: 10.1186/s13059-018-1611-1