Hydrogenated Diglucose Detergents for Membrane-Protein Extraction and Stabilization

We report herein the design and synthesis of a novel series of alkyl glycoside detergents consisting of a nonionic polar headgroup that comprises two glucose moieties in a branched arrangement (DG), onto which octane-, decane-, and dodecanethiols were grafted leading to ODG, DDG, and DDDG detergents...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1985. - 35(2019), 12 vom: 26. März, Seite 4287-4295
1. Verfasser: Guillet, Pierre (VerfasserIn)
Weitere Verfasser: Mahler, Florian, Garnier, Kelly, Nyame Mendendy Boussambe, Gildas, Igonet, Sébastien, Vargas, Carolyn, Ebel, Christine, Soulié, Marine, Keller, Sandro, Jawhari, Anass, Durand, Grégory
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Detergents Membrane Proteins Glucose IY9XDZ35W2
Beschreibung
Zusammenfassung:We report herein the design and synthesis of a novel series of alkyl glycoside detergents consisting of a nonionic polar headgroup that comprises two glucose moieties in a branched arrangement (DG), onto which octane-, decane-, and dodecanethiols were grafted leading to ODG, DDG, and DDDG detergents, respectively. Micellization in aqueous solution was studied by isothermal titration calorimetry, 1H NMR spectroscopy, and surface tensiometry. Critical micellar concentration values were found to decrease by a factor of ∼10 for each pair of methylene groups added to the alkyl chain, ranging from ∼0.05 to 9 mM for DDDG and ODG, respectively. Dynamic light scattering and analytical ultracentrifugation sedimentation velocity experiments were used to investigate the size and composition of the micellar aggregates, showing that the aggregation number significantly increased from ∼40 for ODG to ∼80 for DDDG. All new compounds were able to solubilize membrane proteins (MPs) from bacterial membranes, insect cells, as well as the Madin-Darby canine kidney cells. In particular, native human adenosine receptor (A2AR) and bacterial transporter (BmrA) were solubilized efficiently. Striking thermostability improvements of +13 and +8 °C were observed when ODG and DDG were, respectively, applied to wild-type and full-length A2AR. Taken together, this novel detergent series shows promising detergent potency for solubilization and stabilization of membrane proteins (MPs) and thus makes a valuable addition to the chemical toolbox available for extracting and handling these important but challenging MP targets
Beschreibung:Date Completed 09.07.2020
Date Revised 09.07.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1520-5827
DOI:10.1021/acs.langmuir.8b02842