Lipid-oligonucleotide conjugates (LONs) possess unique amphiphilic and self-organizing properties and display an ability to interact with phospholipid bilayer via noncovalent hydrophobic interactions. This property allows programmable modifications of cellular or bacterial membrane or even plasma membranes in living organisms. However, despite their interesting properties, the synthetic pathways are limited.
A multidisciplinary team led by Tomáš Kraus from IOCB Prague and Michal Hocek from IOCB Prague and Charles University designed and synthesized a series of 2’-deoxyribonucleoside triphosphates (dNTPs) bearing various lipid moieties (fatty acid and cholesterol). The modified dNTPs were enzymatically incorporated into DNA producing either single-stranded or double-stranded LONs containing one or even several lipid units.
In collaboration with Erika Kužmová, the scientists further studied the interactions of such oligonucleotide-lipid probes with the plasma membranes of live cells. The LONs with two cholesterol moieties or a combination of palmitate and cholesterol anchored efficiently and were persistent in the plasma membrane. In addition, some of the probes were detected on the cell surface even after 24 h upon the probe solution removal, which was general to several studied cell lines.
This work is the first report on LONs containing two different lipid moieties and opens pathways for constructing and exploring novel programmable materials for membrane modification and sensing. The results were published as an Edge Article in Chemical Science with David Kodr as the first author.
Read the paper: Kodr, D.; Kužmová, E.; Pohl, R.; Kraus, T.; Hocek, M. Lipid-linked nucleoside triphosphates for enzymatic synthesis of hydrophobic oligonucleotides with enhanced membrane anchoring efficiency. Chem. Sci. 2023. https://doi.org/10.1039/D2SC06718H
