[New Zwitter-Ionic Oligonucleotides: Preparation and Complementary Binding].

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Biochemistry

Context:

• Oligonucleotide synthesis is crucial for developing novel therapeutics.
• Incorporating modified nucleobases can enhance drug properties.
• Zwitter-ionic modifications offer unique physicochemical characteristics.

Purpose:

• To synthesize novel zwitter-ionic oligonucleotide derivatives.
• To evaluate the stability and properties of these modified oligonucleotides.
• To explore their potential as antisense therapeutic agents.

Summary:

• New zwitter-ionic oligonucleotide derivatives featuring a 1,2,3,4-tetrahydroisoquinoline-7-sulfonyl phosphoramidate (THIQ) group were successfully synthesized using automated solid-phase synthesis.
• The THIQ group demonstrated stability throughout standard oligonucleotide synthesis and deprotection steps.
• Modified oligonucleotides exhibited zwitter-ionic properties, altered PAGE mobility, and maintained duplex thermal stability comparable to natural DNA.

Impact:

• This research introduces a novel class of modified oligonucleotides with potential therapeutic applications.
• The developed THIQ modification offers a stable and versatile approach for oligonucleotide functionalization.
• These findings pave the way for advanced antisense oligonucleotide drug development.