title: Mesitylene-Cored Glucoside Amphiphiles (MGAs) for Membrane Protein Studies: Importance of Alkyl Chain Density in Detergent Efficacy.
abstract: Detergents serve as useful tools for membrane protein structural and functional studies. Their amphipathic nature allows detergents to associate with the hydrophobic regions of membrane proteins whilst maintaining the proteins in aqueous solution. However, widely used conventional detergents are limited in their ability to maintain the structural integrity of membrane proteins and thus there are major efforts underway to develop novel agents with improved properties. We prepared mesitylene-cored glucoside amphiphiles (MGAs) with three alkyl chains and compared these agents with previously developed xylene-linked maltoside agents (XMAs) with two alkyl chains and a conventional detergent (DDM). When these agents were evaluated for four membrane proteins including a G protein-coupled receptor (GPCR), some agents such as MGA-C13 and MGA-C14 resulted in markedly enhanced stability of membrane proteins compared to both DDM and the XMAs. This favourable behaviour is due likely to the increased hydrophobic density provided by the extra alkyl chain. Thus, this study not only describes new glucoside agents with potential for membrane protein research, but also introduces a new detergent design principle for future development.
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 15588, Korea.
authors.forename: Kyung Ho
authors.identifier: http://orcid.org/0000-0001-6038-0816
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Orquidea
authors.identifier: http://orcid.org/0000-0003-0746-6666
authors.initials: O
authors.lastname: Ribeiro
authors.affiliation: Molecular and Cellular Physiology, Stanford, CA, 94305, USA.
authors.forename: Yang
authors.identifier: http://orcid.org/0000-0001-5115-0736
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Elena
authors.identifier: http://orcid.org/0000-0002-7892-9173
authors.initials: E
authors.lastname: Tikhonova
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Jonas S
authors.identifier: http://orcid.org/0000-0002-6743-276X
authors.initials: JS
authors.lastname: Mortensen
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Markham
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Parameswaran
authors.identifier: http://orcid.org/0000-0002-6020-1547
authors.initials: P
authors.lastname: Hariharan
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Claus J
authors.identifier: http://orcid.org/0000-0002-1773-1446
authors.initials: CJ
authors.lastname: Loland
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Lan
authors.identifier: http://orcid.org/0000-0002-2274-361X
authors.initials: L
authors.lastname: Guan
authors.affiliation: Molecular and Cellular Physiology, Stanford, CA, 94305, USA.
authors.forename: Brian K
authors.identifier: http://orcid.org/0000-0001-5958-3990
authors.initials: BK
authors.lastname: Kobilka
authors.affiliation: Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Bernadette
authors.identifier: http://orcid.org/0000-0001-9598-9832
authors.initials: B
authors.lastname: Byrne
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 15588, Korea.
authors.forename: Pil Seok
authors.identifier: http://orcid.org/0000-0003-1799-3304
authors.initials: PS
authors.lastname: Chae
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry*; D003902:Detergents / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry*; D014992:Xylenes / Q000737:chemistry*
chemical_list: D001555:Benzene Derivatives; D003902:Detergents; D005960:Glucosides; D008565:Membrane Proteins; D014992:Xylenes; C010219:mesitylene
keywords: amphiphile design; detergents; membrane proteins; protein solubilisation; protein stabilization