Jan 18, 2020

Efficient DNA Condensation by a C3 -Symmetric Codeine Scaffold

Natasha McStayAndrew Kellett


A novel tripodal codeine scaffold (CC3) was rationally designed using computational methods as a DNA condensing alkaloid. Separation of the piperidine nitrogen atoms in CC3 is considerably larger at 14.36 Å than previously reported tripodal opioids allowing for enhanced aggregation of larger DNA plasmids (>4,000 bp). The scaffold undergoes protonation at physiological pH that allows for controlled compaction and release of nucleic acids. Condensation is inhibited under basic conditions and nucleic acid release can be achieved by modulating the ionic strength. Zeta potential experiments indicate stabilised DNA particles at low alkaloid loading with AFM measurements showing particles sizes with a height of 103 nm and diameter of 350 nm. Since condensation is a prerequisite for the cellular uptake of DNA, this new class of alkaloid represents a novel nucleic acid condensation agent with potential gene therapy applications.

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Mentioned in this Paper

HTATIP2 gene
Gene Therapy
Computational Technique
Plant alkaloid
Nucleic Acids
Protein Aggregation, Pathological

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