Nucleobase Modification

Oligonucleotide therapeutics have great potential in the therapeutic areas of cancer, acquired immune diseases, congenital genetic disorders, and others. However, a major obstacle to the widespread use of oligonucleotide therapeutics is how to effectively deliver them to target organs and tissues other than the liver. Therefore, it is necessary to develop different delivery systems in practical applications to make oligonucleotide therapeutics more effective in diagnosing and treating diseases.

Common Nucleobase Modification

Generally speaking, nucleobase modification includes adenine methylation and deamination, cytosine methylation, hydroxymethylation and carboxy substitution, guanine oxidation, etc^[1]. A few specific examples are listed below.

• The 5-methyl group on pyrimidine nucleobases (thymine and 5-methyl cytosine) enhances the thermal stability of oligonucleotide duplexes, which is due to the ability of the methyl group to stack between the planar nucleobases in the major groove. Study shows that introduction of the 5-methyl group on cytosine can reduce the immunostimulatory profile of certain oligonucleotides and also enhance nuclease stability.
• The success of 5-methyl substitution has led to the preparation and evaluation of a number of analogs to improve the affinity of oligonucleotides for complementary RNA. For example, Matteucci introduced a propynyl group at the C-5 position of pyrimidine nucleobases, relative to C-5 methyl substitution, which further improved the stability of the oligonucleotide duplexes. The C-5 position of cytosine nucleobases can also be replaced with a phenoxazine ring that retains the ability to form Watson-Crick base pairings.
• The introduction of 2-thio-deoxythymidine (2-thio-dT) at specific locations within the gap region affects the cleavage pattern of human RNase H for matched and mismatched RNA/antisense oligonucleotide (ASO) duplexes corresponding to the duplexes formed between the ASO and the mutant and wildtype huntingtin transcripts. For example, Ostergaard et al^[2]. recently showed that site-specific incorporation of 2-thio dT can modulate the allele selectivity of ASO targeting single nucleotide polymorphisms for the treatment of Huntington's disease.

What We Offer?

As the world's leading explorer of oligonucleotide therapeutics, Alfa Chemistry provides our customers with nucleobase modification services for therapeutic oligonucleotides. You can also contact us to customize any nucleobase-modified oligonucleotide you need.

Why Choose Us?

• Experienced experts
• Extensive chemical modification technologies
• Advanced analytical equipment
• Professional technical advice
• Competitive price
• Fast delivery

Our products and services are for research use only and cannot be used for any clinical purposes.

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