title: Design of new fluorescent cholesterol and ergosterol analogs: Insights from theory.
abstract: Cholesterol (Chol) and ergosterol (Erg) are abundant and important sterols in the plasma membrane of mammalian and yeast cells, respectively. The effects of Chol and Erg on membrane properties, as well as their intracellular transport, can be studied with use of fluorescence probes mimicking both sterols as closely as possible. In the search for new and efficient Chol and Erg probes, we use a combination of theoretical methods to explore a series of analogs. The optical properties of the analogs (i.e. excitation energies, emission energies and oscillator strengths) are examined using time-dependent density functional theory (TDDFT) and their ability to mimic the effects of Chol and Erg on membranes is investigated with molecular dynamics (MD) simulations of each analog in a 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayer. From the set of analogs we find two probes (3a and 3b) to display favorable electronic transition properties as well as strong condensing abilities. These findings can lead to the use of new efficient probes and aid in the understanding of the structural features of Chol and Erg that impart to them their unique effects on lipid membranes.
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark. Electronic address: naabo@sdu.dk.
authors.forename: Lina J
authors.initials: LJ
authors.lastname: Nåbo
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
authors.forename: Nanna H
authors.initials: NH
authors.lastname: List
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
authors.forename: Sarah
authors.initials: S
authors.lastname: Witzke
authors.affiliation: Department of Biochemistry and Molecular Biology, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wüstner
authors.affiliation: MEMPHYS - Center for Biomembrane Physics, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Khandelia
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark. Electronic address: kongsted@sdu.dk.
authors.forename: Jacob
authors.initials: J
authors.lastname: Kongsted
mesh_terms: D002784:Cholesterol / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D015195:Drug Design; D004875:Ergosterol / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D005456:Fluorescent Dyes / Q000138:chemical synthesis*; D008051:Lipid Bilayers / Q000737:chemistry*; D008422:Materials Testing; D056004:Molecular Dynamics Simulation
chemical_list: D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D002784:Cholesterol; D004875:Ergosterol
keywords: Cholesterol; Ergosterol; Fluorescence probe; Lipid bilayer; Molecular dynamics simulation; Time-dependent DFT