DOTAP: Structure, hydration, and the counterion effect.

Autor:	Mihailescu M; Institute for Bioscience and Biotechnology Research, Rockville, Maryland. Electronic address: ella11@umd.edu., Worcester DL; Biology Division, University of Missouri, Columbia, Missouri; NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland; Department of Physiology and Biophysics, University of California at Irvine, Irvine, California., Carroll CL; Department of Chemistry, University of California at Irvine, Irvine, California., Chamberlin AR; Department of Chemistry, University of California at Irvine, Irvine, California; Department of Pharmaceutical Sciences, University of California at Irvine, Irvine, California., White SH; NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland; Department of Physiology and Biophysics, University of California at Irvine, Irvine, California.
Jazyk:	angličtina
Zdroj:	Biophysical journal [Biophys J] 2023 Mar 21; Vol. 122 (6), pp. 1086-1093. Date of Electronic Publication: 2023 Jan 26.
DOI:	10.1016/j.bpj.2023.01.031
Abstrakt:	The cationic lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) is one of the original synthetic cationic lipids used for the liposomal transfection of oligonucleotides in gene therapy. The key structural element of DOTAP is its quaternary ammonium headgroup that is responsible for interactions with both nucleic acids and target cell membranes. Because these interactions are fundamental to the design of a major class of transfection lipids, it is important to understand the structure of DOTAP and how it interacts with halide counterions. Here, we use x-ray and neutron diffraction techniques to examine the structure of DOTAP and how chloride (Cl-) and iodide (I-) counterions alter the hydration properties of the DOTAP headgroup. A problem of particular interest is the poor solubility of DOTAP/I- in water solutions. Our results show that the poor solubility results from very tight binding of the I- counterion to the headgroup and the consequent expulsion of water. The structural principles we report here are important for assessing the suitability of DOTAP and its quaternary ammonium derivatives for transfection. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Biophysical Society. All rights reserved.)
Databáze:	MEDLINE
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