Advances in Detergent Research

Introduction

Detergents are capable of mediating contacts between surfaces differing in polarity, such as hydrophilic and hydrophobic surfaces. In contrast to other surfactants, detergents can destabilize and even solubilize the membrane lipid bilayer. Detergents play an important role and have been widely used in biochemical field, especially in the study of membrane protein. Traditional detergents can be divided into anionic detergents, cationic detergents, non-ionic detergents and zwitterionic detergents. The limited structural miscellany of conventional detergents is in stark contrast with the far-reaching diversity of membrane proteins. Thus, the development of some novel detergents that may be employed to study a wider array of membrane proteins has attracted the wide attention of peoples.

Novel Detergents– Current Development

The past researches mainly focused on the evolution of detergent classes, via the introduction and modification of functional groups, to confer improved their properties. However, recently there has been a drive towards developing completely novel detergents that confer, in particular, elevated protein stability, compared with classical detergents ^[1]. Examples of these include: a new class of steroid-based penta-saccharides, fluorinated glucose and maltose-based detergents, innovative facial amphiphiles (FAs), 1,3,5-triazine-cored detergents and disulfide containing amphiphiles.

• Steroid-based penta-saccharides: Ehsan et. al prepared three sets of steroid-based amphiphiles. One set contains two maltoside head groups directly connected onto diosgenin hydrophobic group, designated GDN analogs, while the other two sets contain a penta-saccharide group connected with four different steroidal groups either directly (steroid-based penta-saccharides (SPSs)) or via a linker (SPS-Ls). These novel detergents, particularly the SPS-Ls, displayed favorable behaviors with the tested membrane proteins ^[2].

Fig. 1. The chemical structures of the SPSs.

• Fluorinated glucose and maltose-based detergents: Boussambe et. al developed new fluorinated detergents. The detergents contain two glucose moieties as polar headgroup, a hydrogenated thioether linker, and a perfluorinated alkyl tail with either 4, 6, or 8 carbon atoms. The developed fluorinated detergents exhibited detergency in terms of both lipid-vesicle solubilization and membrane-protein extraction ^[3]. Wehbie et. al designed two new fluorinated detergents, F5OM and F5DM, which were designed as partially fluorinated analogues of n-dodecyl-β-D-maltoside (DDM). The study indicated both extracting and stabilizing properties of the new fluorinated maltose-based detergents, making them promising tools in membrane proteins applications ^[4].
• Innovative facial amphiphiles: Das et. al introduced a series of lithocholate-based facial amphiphiles (designated LFAs) bearing a flexible alkyl pendant at the end of the lithocholate skeleton. Because of the presence of the flexible alkyl pendant, the LFAs have enhanced conformational flexibility, which facilitates detergent interaction with hydrophobic protein surfaces ^[5]. A new family of tandem facial glucosides/maltosides (TFGs/TFMs) for membrane protein manipulation was also prepared by Das et. al. The ether-based TFMs (TFM-C0E, TFM-C3E or TFM-C5E) were notable for their ability to confer enhanced membrane protein stability compared to the previously developed amide-based tandem facial amphiphiles (TFAs) ^[6].

Fig. 2. The chemical structures of the LFAs-C4 (the representative product of LFAs).

• 1,3,5-triazine-cored detergents: Ghani et. al. designed and synthesized 1,3,5-triazine-cored dimaltoside amphiphiles derived from cyanuric chloride. By introducing variations in the alkyl chain linkage and an amine-functionalized diol linker, they prepared two sets of 1,3,5-triazine-based detergents. These detergents showed significant potential for membrane protein study as a consequence of their structural diversity and universal stabilization efficacy for three transporters and two G protein-coupled receptors ^[7].

Fig. 3. The chemical structures of one of representative products of 1,3,5-triazine-based detergents.

• Disulfide containing amphiphiles: Xue et. al. introduced disulfide-containing detergents (DCDs), which contain a disulfide bond in the hydrophobic tail. The synthesis of DCDs commenced from the glycosylation of the readily available peracetylated maltoside with the appropriate alcohols with terminal bromide. The DCDs form smaller micelles than corresponding detergents with linear hydrocarbon chains, while providing good solubilization and reconstitution of membrane proteins ^[8].
• Others: Other examples of novel detergents developed in recently include modified neopentyl glycol based detergents, vitamin-E based glycoside amphiphiles (VEGs), calixarene based detergents and others ^[9-11].

At Alfa Chemistry, we deliver a wide range of high-quality detergents, including anionic detergents, cationic detergents, non-ionic detergents, zwitterionic detergents and deuterated detergents. In addition, we also offer some special and novel detergents such as neopentyl-based glycosides, fluorinated detergents, tripod detergents, seleniated detergents and others. It is worth mentioning that the extensive detergents kits can be found in our product inventory that can simplify the process of screening the optimal detergents. If you don't find the product you want, we can tailor reagents to meet the needs of our consumers. We are also willing to cooperate with you to develop new and efficient detergent products. Please don't hesitate to contact us, if you are in need of assistance.

References

1. Ratkeviciute G., et al. Methods for the solubilisation of membrane proteins: the micelle-aneous world of membrane protein solubilisation[J]. Biochemical Society Transactions, 2021, 49(4): 1763-1777.
2. Ehsan M., et al. Steroid‐based amphiphiles for membrane protein study: The importance of alkyl spacers for protein stability[J]. ChemBioChem, 2018, 19(13): 1433-1443.
3. Boussambe G. N. M., et al. Fluorinated diglucose detergents for membrane-protein extraction[J]. Methods, 2018, 147: 84-94.
4. Wehbie M., et al. Maltose-based fluorinated surfactants for membrane-protein extraction and stabilization[J]. Langmuir, 2021, 37(6): 2111-2122.
5. Das M., et al. An Engineered Lithocholate‐based facial amphiphile stabilizes membrane proteins: assessing the impact of detergent customizability on protein stability[J]. Chemistry–A European Journal, 2018, 24(39): 9860-9868.
6. Das M., et al. Rationally engineered tandem facial amphiphiles for improved membrane protein stabilization efficacy[J]. ChemBioChem, 2018, 19(20): 2225-2232.
7. Ghani L., et al. 1, 3, 5-Triazine-cored maltoside amphiphiles for membrane protein extraction and stabilization[J]. Journal of the American Chemical Society, 2019, 141(50): 19677-19687.
8. Xue D., et al. Disulfide‐containing detergents (DCDs) for the structural biology of membrane proteins[J]. Chemistry–A European Journal, 2019, 25(50): 11635-11640.
9. Bae H. E., et al. Asymmetric maltose neopentyl glycol amphiphiles for a membrane protein study: effect of detergent asymmetricity on protein stability[J]. Chemical science, 2019, 10(4): 1107-1116.
10. Ehsan M., et al. Vitamin E-based glycoside amphiphiles for membrane protein structural studies[J]. Organic & Biomolecular Chemistry, 2018, 16(14): 2489-2498.
11. Dauvergne J., et al. Glycosylated amphiphilic calixarene‐based detergent for functional stabilization of native membrane proteins[J]. ChemistrySelect, 2019, 4(19): 5535-5539.

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