Nucleosides with Transposed Base or 4'-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

Area of Science:

• Medicinal Chemistry
• Nucleoside Chemistry
• Oligonucleotide Therapeutics

Background:

• Modified nucleosides, including 4'-hydroxymethyl and nucleobase-transposed analogues, are investigated for therapeutic potential.
• These compounds and their derivatives exhibit promising biological activities relevant to antiviral and anticancer drug discovery.

Purpose of the Study:

• To compile and review the biological activities of 4'-hydroxymethyl- or nucleobase-transposed nucleosides, nucleotides, and nucleoside phosphonates.
• To describe synthetic routes, including innovative strategies, for these nucleoside derivatives.
• To discuss the properties and applications of oligonucleotides containing these modified nucleotides.

Main Methods:

• Literature review of chemical and enzymatic synthesis strategies.
• Compilation and analysis of biological activity data (antiviral, anticancer).
• Discussion of structural, base-pairing, and stability properties of modified oligonucleotides.

Main Results:

• Comprehensive overview of known 4'-hydroxymethyl- and nucleobase-transposed nucleosides, nucleotides, and phosphonates.
• Detailed description of synthetic methodologies and innovative approaches.
• Exploration of modified oligonucleotides for therapeutic applications, including inhibition of viral integrase and use in antisense therapy, siRNA, and aptamer selection.

Conclusions:

• Modified nucleosides represent a valuable class of compounds with significant potential in antiviral and anticancer therapies.
• Innovative synthetic strategies are crucial for accessing these complex molecules.
• Oligonucleotides incorporating these modified nucleosides show promise for targeted therapeutic interventions.