Hydrophobic variants of ganglio-tripod amphiphiles for membrane protein manipulation

Chae, Pil Seok; Cho, Kyung Ho; Wander, Marc J.; Bae, Hyoung Eun; Gellman, Samuel H.; Laible, Philip D.

doi:10.1016/j.bbamem.2013.09.011

Cited by 29 publications

(13 citation statements)

References 61 publications

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“…In addition, as emerged from our TPA studies, the branched diglucoside group has better membrane protein stabilising properties. We previously observed that branched diglucoside‐bearing TPAs were superior to maltoside‐bearing TPAs for stabilising LHI–RC complexes 26a. A similar trend was observed for DCGs in the current study.…”

Section: Methodssupporting

confidence: 89%

Deoxycholate‐Based Glycosides (DCGs) for Membrane Protein Stabilisation

et al. 2015

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Detergents are an absolute requirement for studying the structure of membrane proteins. However, many conventional detergents fail to stabilise denaturation-sensitive membrane proteins, such as eukaryotic proteins and membrane protein complexes. New amphipathic agents with enhanced efficacy in stabilising membrane proteins will be helpful in overcoming the barriers to studying membrane protein structures. We have prepared a number of deoxycholate-based amphiphiles with carbohydrate head groups, designated deoxycholate-based glycosides (DCGs). These DCGs are the hydrophilic variants of previously reported deoxycholate-based N-oxides (DCAOs). Membrane proteins in these agents, particularly the branched diglucoside-bearing amphiphiles DCG-1 and DCG-2, displayed favourable behaviour compared to previously reported parent compounds (DCAOs) and conventional detergents (LDAO and DDM). Given their excellent properties, these agents should have significant potential for membrane protein studies.

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Section: Methodssupporting

confidence: 89%

Deoxycholate‐Based Glycosides (DCGs) for Membrane Protein Stabilisation

et al. 2015

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“…Many novel agents have been developed over the past two decades, to address the narrow scope of utility of conventional detergents. These include small amphipathic agents such as tripod amphiphiles (TPAs),, glyco‐diosgenin (GDN), and hemifluorinated surfactants (HFSs), neopentyl glycol‐derived triglucosides (NDTs), medium‐sized peptide‐based amphiphiles (e.g., lipopeptide detergents (LPDs), short peptides and β‐peptides (BPs)) as well as large nanoassemblies such as amphipols (Apols),, nanodiscs (NDs) and nanolipodisqs . Facial amphiphiles (FAs)– glucose or maltose neopentyl glycols (GNGs or MNGs)– are particularly attractive because these agents have been highly successful in membrane protein structural study.…”

Section: Methodsmentioning

confidence: 99%

Accessible Mannitol‐Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation

Hussain

Scull

et al. 2016

Chemistry A European J

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Integral membrane proteins are amphipathic molecules crucial for all cellular life. The structural study of these macromolecules starts with protein extraction from the native membranes, followed by purification and crystallisation. Detergents are essential tools for these processes, but detergent-solubilised membrane proteins often denature and aggregate, resulting in loss of both structure and function. In this study, a novel class of agents, designated mannitol-based amphiphiles (MNAs), were prepared and characterised for their ability to solubilise and stabilise membrane proteins. Some of MNAs conferred enhanced stability to four membrane proteins including a G protein-coupled receptor (GPCR), the β2 adrenergic receptor (β2AR), compared to both n-dodecyl-D-maltoside (DDM) and the other MNAs. These agents were also better than DDM for electron microscopy analysis of the β2AR. The ease of preparation together with the enhanced membrane protein stabilisation efficacy demonstrates the value of these agents for future membrane protein research.

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“…However, they have a number of disadvantages: they tend to form large protein-detergent complexes (PDCs), are often ineffective at efficiently extracting proteins from the membranes, and are often difficult to synthesize on a bulk scale. In contrast, small amphipathic agents have also been developed as exemplified by tripod amphiphiles (TPAs), 15 facial amphiphiles (FAs), 16 neopentyl glycol (NG) class amphiphiles (GNGs 17 or MNGs), 18 mannitol-based amphiphiles (MNAs), 19 neopentyl glycol triglucosides (NDTs), 20 and penta-saccharide amphiphiles (PSEs). 21 These can all be easily synthesized and are largely as effective as DDM at extracting proteins from the membrane.…”

Section: Introductionmentioning

confidence: 99%

Conformationally Preorganized Diastereomeric Norbornane-Based Maltosides for Membrane Protein Study: Implications of Detergent Kink for Micellar Properties

Das

Ribeiro

et al. 2017

J. Am. Chem. Soc.

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Detergents are essential tools for functional and structural studies of membrane proteins. However, conventional detergents are limited in their scope and utility, particularly for eukaryotic membrane proteins. Thus, there are major efforts to develop new amphipathic agents with enhanced properties. Here, a novel class of diastereomeric agents with a preorganized conformation, designated norbornane-based maltosides (NBMs), were prepared and evaluated for their ability to solubilize and stabilize membrane proteins. Representative NBMs displayed enhanced behaviors compared to n-dodecyl-β-d-maltoside (DDM) for all membrane proteins tested. Efficacy of the individual NBMs varied depending on the overall detergent shape and alkyl chain length. Specifically, NBMs with no kink in the lipophilic region conferred greater stability to the proteins than NBMs with a kink. In addition, long alkyl chain NBMs were generally better at stabilizing membrane proteins than short alkyl chain agents. Furthermore, use of one well-behaving NBM enabled us to attain a marked stabilization and clear visualization of a challenging membrane protein complex using electron microscopy. Thus, this study not only describes novel maltoside detergents with enhanced protein-stabilizing properties but also suggests that overall detergent geometry has an important role in determining membrane protein stability. Notably, this is the first systematic study on the effect of detergent kinking on micellar properties and associated membrane protein stability.

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Hydrophobic variants of ganglio-tripod amphiphiles for membrane protein manipulation

Cited by 29 publications

References 61 publications

Deoxycholate‐Based Glycosides (DCGs) for Membrane Protein Stabilisation

Deoxycholate‐Based Glycosides (DCGs) for Membrane Protein Stabilisation

Accessible Mannitol‐Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation

Conformationally Preorganized Diastereomeric Norbornane-Based Maltosides for Membrane Protein Study: Implications of Detergent Kink for Micellar Properties

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