Structural design of intrinsically fluorescent oxysterols

Lina J Nåbo, Maciej Modzel, Kathiresan Krishnan, Douglas F Covey, Hideji Fujiwara, Daniel S Ory, Maria Szomek, Himanshu Khandelia, Daniel Wüstner, Jacob Kongsted

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Abstract

Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside a membrane is analyzed and compared with that of 25-hydroxycholesterol using molecular dynamics simulations. The analogs' one- and two-photon absorption properties inside the membrane are evaluated using electronic structure calculations with polarizable embedding. Due to predicted keto-enol tautomerisation of the new oxysterol analog, we also evaluate the keto form. Both analogs are found to be good probe candidates for 25-hydroxycholesterol, provided that the new analog remains in the enol-form. Only the new analog with extended conjugated system shows significant two-photon absorption, which is strongly enhanced by the presence of the membrane.

Original languageEnglish
JournalChemistry and Physics of Lipids
Volume212
Pages (from-to)26–34
ISSN0009-3084
DOIs
Publication statusPublished - 2018

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Structural design
Photons
Membranes
Fluorescence microscopy
Electronic structure
Molecular dynamics
Fluorescence
Cholesterol
Derivatives
Computer simulation
Molecular Dynamics Simulation
Fluorescence Microscopy
25-hydroxycholesterol
Observation

Keywords

  • Journal Article

Cite this

Nåbo, L. J., Modzel, M., Krishnan, K., Covey, D. F., Fujiwara, H., Ory, D. S., ... Kongsted, J. (2018). Structural design of intrinsically fluorescent oxysterols. Chemistry and Physics of Lipids, 212, 26–34. https://doi.org/10.1016/j.chemphyslip.2017.12.005
Nåbo, Lina J ; Modzel, Maciej ; Krishnan, Kathiresan ; Covey, Douglas F ; Fujiwara, Hideji ; Ory, Daniel S ; Szomek, Maria ; Khandelia, Himanshu ; Wüstner, Daniel ; Kongsted, Jacob. / Structural design of intrinsically fluorescent oxysterols. In: Chemistry and Physics of Lipids. 2018 ; Vol. 212. pp. 26–34.
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abstract = "Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside a membrane is analyzed and compared with that of 25-hydroxycholesterol using molecular dynamics simulations. The analogs' one- and two-photon absorption properties inside the membrane are evaluated using electronic structure calculations with polarizable embedding. Due to predicted keto-enol tautomerisation of the new oxysterol analog, we also evaluate the keto form. Both analogs are found to be good probe candidates for 25-hydroxycholesterol, provided that the new analog remains in the enol-form. Only the new analog with extended conjugated system shows significant two-photon absorption, which is strongly enhanced by the presence of the membrane.",
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Structural design of intrinsically fluorescent oxysterols. / Nåbo, Lina J; Modzel, Maciej; Krishnan, Kathiresan; Covey, Douglas F; Fujiwara, Hideji; Ory, Daniel S; Szomek, Maria; Khandelia, Himanshu; Wüstner, Daniel; Kongsted, Jacob.

In: Chemistry and Physics of Lipids, Vol. 212, 2018, p. 26–34.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Structural design of intrinsically fluorescent oxysterols

AU - Nåbo, Lina J

AU - Modzel, Maciej

AU - Krishnan, Kathiresan

AU - Covey, Douglas F

AU - Fujiwara, Hideji

AU - Ory, Daniel S

AU - Szomek, Maria

AU - Khandelia, Himanshu

AU - Wüstner, Daniel

AU - Kongsted, Jacob

N1 - Copyright © 2017. Published by Elsevier B.V.

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N2 - Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside a membrane is analyzed and compared with that of 25-hydroxycholesterol using molecular dynamics simulations. The analogs' one- and two-photon absorption properties inside the membrane are evaluated using electronic structure calculations with polarizable embedding. Due to predicted keto-enol tautomerisation of the new oxysterol analog, we also evaluate the keto form. Both analogs are found to be good probe candidates for 25-hydroxycholesterol, provided that the new analog remains in the enol-form. Only the new analog with extended conjugated system shows significant two-photon absorption, which is strongly enhanced by the presence of the membrane.

AB - Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside a membrane is analyzed and compared with that of 25-hydroxycholesterol using molecular dynamics simulations. The analogs' one- and two-photon absorption properties inside the membrane are evaluated using electronic structure calculations with polarizable embedding. Due to predicted keto-enol tautomerisation of the new oxysterol analog, we also evaluate the keto form. Both analogs are found to be good probe candidates for 25-hydroxycholesterol, provided that the new analog remains in the enol-form. Only the new analog with extended conjugated system shows significant two-photon absorption, which is strongly enhanced by the presence of the membrane.

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