Glucose-Neopentyl Glycol (GNG) amphiphiles for membrane protein study

Abstract

The development of a new class of surfactants for membrane protein manipulation, “GNG amphiphiles”, is reported. These amphiphiles display promising behavior for membrane proteins, as demonstrated recently by the high resolution structure of a sodium-pumping pyrophosphatase reported by Kellosalo et al.

Maltose neopentyl glycol-3 (MNG-3) analogues for membrane protein study

“…11 Good examples include tripod amphiphiles (TPAs) with three hydrophobic groups, 11a–d hemifluorinated surfactants (HFSs) containing a fluorinated alkyl chain, 11e facial amphiphiles (FAs) derived from cholic/deoxycholic acid, 11f,g rigid hydrophobic group-bearing amphiphiles (chobimalt and glyco-diosgenin (GDN)) with a multi-fused ring in the lipophilic portion, 11h,i glucose or maltose-neopentyl glycols (GNGs and MNGs) with branched diglucoside or maltoside head group, 11j–m and calixarene-based ionic surfactants. 11n The secondary peptide structures have proved popular as scaffolds for novel amphiphile development. 12 The α-helix forming peptides such as peptitergent 12a and lipopeptide detergents (LPDs) 12b are the most well-known designs.…”

“…GNG-3 (commercial name: OGNG) was used in the determination of the Na + –pumping pyrophosphatase and human aquaporin 2 (AQZ 2). 14a,b MNG-3 (commercial name: LMNG) 11j has facilitated the high resolution structure determination of more than 10 G–protein coupled receptors such as the β 2 adrenergic receptor (β 2 AR), opioid receptors, muscarinic acetylcholine receptors and the neurotensin receptor 15a–j in addition to the Twin Arginine Translocator, N–methyl–D–aspartate (NMDA) receptor ion channel and Claudin–15 tight junction. 15k–m Furthermore, this agent is shown to confer stability on membrane protein complexes such as the β 2 ARβGs complex and β 2 ARβarrestin–1 complex.…”

Overcoming bottlenecks in the membrane protein structural biology pipeline

“…The difference between these detergents and more conventional detergents with similar structures, such as n-dodecyl β-D-maltoside DDM ( Figure 2C) is the central quaternary carbon atom that is derived from neopentyl glycol allowing for the addition of two hydrophobic and hydrophilic groups [30]. GNG has four different variants and MNG has three with the difference involving the attachment of the hydrophobic chain to the quaternary carbon [31]. Use of GNG-3 has help to produce the structure of Na + -pumping pyrophosphatase [32] and human aquaporin 2 (AQZ 2) [33].…”

Resorcinarene‐Based Facial Glycosides: Implication of Detergent Flexibility on Membrane‐Protein Stability

“…Therefore, it is necessary to develop new detergents with distinct architectures to cope with the diverse range of membrane proteins. Recent representative classes include tripod amphiphiles, [2, 3] lipopeptide detergents, [4] hemifluorinated surfactants, [5] glucose or maltose neopentyl glycols (GNGs or MNGs), [6] glyco-diosgenin, [7] facial amphiphiles, [8] neopentyl glycol-derived triglucosides [9] and penta-saccharide-based amphiphiles. [10] Apart from these small amphiphiles, there are polymeric nano-assemblies (polymeric materials or polymer–lipid superassemblies) such as amphipols, [5, 11] nanodiscs [5, 12] and nanolipodisc particles.…”

“…[1a, 6b] Notably, the current new agents appeared to be even superior to MNG-3, one of the most successful new detergents for membrane-protein studies. [6a] MNG-3 was roughly as effective as DDM at maintaining UapA in a stable state, whereas the current new agents were significantly better (Figure S3 in the Supporting Information). In the case of LeuT, a previous study has indicated that MNG-3 is slightly superior to DDM at maintaining transporter stability.…”