Triazole-linked dumbbell oligodeoxynucleotides with NF-kappaB binding ability as potential decoy molecules

Area of Science:

• Oligonucleotide chemistry
• Molecular biology
• Biochemistry

Background:

• Decoy molecules are crucial for altering gene expression by binding to transcription factors.
• Traditional decoy molecules often lack sufficient stability for therapeutic applications.
• Developing stable and effective decoy molecules is a key challenge in gene regulation research.

Purpose of the Study:

• To synthesize and characterize triazole-cross-linked dumbbell oligodeoxynucleotides.
• To evaluate the stability and binding affinity of these novel oligodeoxynucleotides.
• To determine their potential as decoy molecules for transcription factors like NF-κB.

Main Methods:

• Synthesis of oligodeoxynucleotides using Cu(I) catalyzed alkyne-azide cycloaddition (CuAAC).
• Incorporation of N-3-(azidoethyl)thymidine and N-3-(propargyl)thymidine for cross-linking.
• Assessment of thermal stability and resistance to snake venom phosphodiesterase (3'-exonuclease).
• Evaluation of binding affinity to NF-kappaB p50 homodimer.

Main Results:

• Synthesized oligodeoxynucleotides demonstrated high thermal stability and resistance to exonuclease degradation.
• The triazole cross-linking did not disrupt the global structure of the oligodeoxynucleotides.
• Dumbbell oligodeoxynucleotides exhibited significant binding affinity to NF-kappaB p50 homodimer.
• Binding affinity was modulated by altering the loop length of the dumbbell structure.

Conclusions:

• Triazole cross-linking is a viable strategy to enhance the stability of dumbbell oligodeoxynucleotides.
• These cross-linked molecules retain their ability to bind target transcription factors, specifically NF-κB.
• Triazole cross-linked dumbbell oligodeoxynucleotides show promise as potent decoy molecules for gene expression modulation.