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Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
Published on: February 8, 2017
Tailored hydrophobic cavities in oligonucleotide-steroid conjugates
1Department of Chemistry and Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA. r-letsinger@chem.nwu.edu
Bioconjugate Chemistry
|November 17, 1998
Summary
Researchers created hydrophobic pockets in DNA using steroid conjugates. A specific molecule stabilizes these pockets, offering a new way to control DNA hybridization for potential applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Organic Chemistry
Background:
- Hydrophobic interactions are crucial in molecular recognition.
- Oligonucleotide conjugates offer versatile platforms for designing novel molecular architectures.
- Controlling hybridization in aqueous solutions remains a challenge.
Purpose of the Study:
- To develop a method for creating controllable hydrophobic pockets within oligonucleotide complexes in aqueous solution.
- To investigate the stabilization of these hydrophobic pockets using specific hydrophobic substrates.
- To explore the potential for modulating oligonucleotide hybridization through engineered pockets.
Main Methods:
- Synthesizing oligonucleotide conjugates with embedded androstane units linked by phosphoryl groups.
- Forming double- and triple-stranded DNA complexes with these conjugates.
- Introducing a water-soluble hydrophobic substrate (3,17-diaminoandrostane dihydrochloride) to stabilize the complexes.
- Assessing the effect of the substrate and other agents (1,10-diaminodecane dihydrochloride, Cetyltrimethylammonium bromide) on complex stability and dissociation.
Main Results:
- Hydrophobic pockets were successfully generated in aqueous solution within oligonucleotide conjugate complexes.
- The addition of 3,17-diaminoandrostane dihydrochloride significantly stabilized both double- and triple-stranded complexes by binding to the hydrophobic pockets.
- The stabilizing substrate did not affect the dissociation of unmodified oligonucleotides.
- Cetyltrimethylammonium bromide enhanced the stability of steroid conjugate complexes but caused precipitation of unmodified oligonucleotide complexes.
Conclusions:
- A novel system for creating and stabilizing hydrophobic pockets in oligonucleotide complexes has been established.
- This system allows for selective modulation and triggering of oligonucleotide conjugate hybridization.
- The findings provide a new tool for designing responsive nucleic acid-based systems.
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