Incorporation of fluorophore-cholesterol conjugates into liposomal and mycobacterial membranes

Bioorganic & Medicinal Chemistry
Ashley N WercholukWilliam E Allen

Abstract

Fluorescently-labeled steroids that emit intense blue light in nonpolar solvent (λem (CH2Cl2)≈440nm, ΦF=0.70) were prepared by treating cholesteryl chloroformate with 4-amino-1,8-naphthalimides. The lipid portion of the conjugates embeds into liposomal membrane bilayers in minutes, leaving the fluorophore exposed to the external aqueous environment. This causes a 40-nm red-shift in λem and significant quenching. DFT optimizations predict the conjugates to be about 30Å long when fully extended, but rotation about the linker group can bring the compounds into an 'L'-shape. Such a conformation would allow the cholesteryl anchor to remain parallel to the acyl chains of a membrane while the fluorescent group resides in the interfacial region, instead of extending beyond it. When incubated with Mycobacterium smegmatis mc2 155, a bacterial species known to use natural cholesterol, the labeled steroids support growth and can be found localized in the membrane fraction of the cells using HPLC. These findings demonstrate stable integration of fluorescent cholesterols into bacterial membranes in vivo, indicating that these compounds may be useful for evaluating cholesterol uptake in prokaryotic organisms.

References

Oct 21, 1998·Biochemistry·W M YauS H White
Oct 31, 2006·Bioorganic & Medicinal Chemistry Letters·Keith D CombrinkAnthony S Lynch
Feb 1, 2007·Proceedings of the National Academy of Sciences of the United States of America·Robert Van der GeizeLindsay D Eltis
Mar 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Amit K Pandey, Christopher M Sassetti
Oct 29, 2008·The Journal of Biological Chemistry·William W MohnLindsay D Eltis
Mar 3, 2009·The Journal of Physical Chemistry. B·Sandeep ShrivastavaAmitabha Chattopadhyay
Apr 16, 2009·Journal of the American Chemical Society·Salvador Tomas, Lilia Milanesi
Dec 22, 2009·Organic & Biomolecular Chemistry·Cyril BarsuChantal Andraud
Dec 23, 2009·Biochimica Et Biophysica Acta·Daniel M Carter RamirezLinda J Johnston
Sep 20, 2011·Trends in Microbiology·Hugues OuelletPaul R Ortiz de Montellano
Dec 27, 2011·Chemistry & Biology·Emilie LayreD Branch Moody
Mar 26, 2013·Biomedical Chromatography : BMC·Xiu-zhen CaoJoshi K Manoj
Apr 1, 2012·Environmental Microbiology Reports·Iria UhíaJosé L García
Mar 4, 2014·Current Opinion in Microbiology·François Vromman, Agathe Subtil
Mar 13, 2014·Critical Reviews in Biochemistry and Molecular Biology·Matthew F WippermanSuzanne T Thomas
Jun 6, 2014·Chemical Communications : Chem Comm·Manpreet BhattiSalvador Tomas
Sep 12, 2014·The Journal of Biological Chemistry·Daniel J FrankPaul R Ortiz de Montellano

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Citations

Oct 27, 2016·Steroids·Yaroslav FaletrovVladimir Shkumatov
Aug 17, 2018·Photochemistry and Photobiology·Goutam GhoshAlexander Greer
Jan 2, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hélio M T AlbuquerqueArtur M S Silva

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