The most important part of setting higher standards
comes down to one word: Innovation

The substantial use of Dodecyl-ß-D-Maltoside (DDM, D310) and Lauryl Maltose Neopentyl Glycol (LMNG, NG310) for the solubilization, purification, and crystallization of membrane proteins suggests that the combination of a disaccharide linked to a 12-carbon alkyl tail is important to the stabilization of these proteins (see our February, 2016 newsletter for more information about the use of these, and other, detergents in membrane protein biochemistry). Based on this evidence, this year we have been focusing on launching new detergents with variations to this basic architecture. In April of this year, we launched our new Dodecyl Trehaloside (DDTre) detergents(1), which replace the disaccharide maltose with a trehalose. This month, further expanding on this theme, we are launching two new classes of detergents: Monopodal Amphiphiles (MPA), which are variations to the Maltoside molecular architecture and a Mannitol-Based Amphiphile (MNA), which is a variation to the molecular architecture of the Neopentyl Glycols.
 
First described in the original paper for the LMNG detergents(2), the MPA-4 class of detergents vary the molecular architecture of the maltoside class of detergents by adding an oxypropyl group between the maltose disaccharide and the alkyl chain. The two new MPA-4 detergents differ in the length of the alkyl chain. MPA4-C10 links the oxypropyl group to a ten carbon alkyl chain, while MPA4-C12 links the oxypropyl group to a twelve carbon alkyl chain. Molecular weight and CMC data for MPA4-C10 and MPA4-C12 can be found in the table below. In this paper, MPA-4-C10 was tested on the thermostability of three membrane proteins using the CPM assay(3): succinate:quinone oxidoreductase (SQR), cytochrome bo3 , and the cytidine-5′-monophosphate–sialic acid transporter (CMP-Sia). For all three of these proteins, MPA-4-C10 performed similarly to DDM, and were nearly as effective as LMNG. 
 
Recently developed by the labs of Brian Kobilka and Pil-Seok Chae(4), the MNA class of detergents are a variation to the neopentyl glycol class of detergents. MNA-C12 has two flexible twelve carbon alkyl chains connected to four glucose groups via a mannitol linker. Molecular weight and CMC data for MNA-C12 can be found in the table below. The performance of MNA-C12 was tested on four membrane proteins: boron transporter (BOR1), leucine transporter (LeuT), light-harvesting complex I from Rhodobacter capsulatus (LHI-RC), and human b2 adrenergic receptor (b2AR). For BOR1, MNA-C12 showed better solubilization efficiency and thermostability when compared to DDM. For LeuT and LHI-RC, MNA-C12 showed increased long term stability of the proteins when compared to DDM. Lastly, b2AR showed similar activation activity MNA-C12 compared to DDM; however, assays performed at detergent concentrations far below the CMCs suggest that MNA-C12 forms stronger interactions with the protein compared to DDM, and produce protein-detergent complexes more resistant to reductions in detergent concentration. 

 

Figure 1:New MPA-4 and MNA detergents.

 



Other detergents in the MNA family, MNA-C13 and MNA-C14, will be available later this year. Check out our New Products Coming Soon page for more information. 


Table 1: Properties of new MPA4 and MNA detergents compared to DDM

Detergent MW CMC (mM) CMC (%)
MPA4-C10 540.64 0.660 0.036
MPA4-C12 568.69 ~0.06 ~0.0032
MNA-C12 1167.4 0.004 0.0005
DDM 510.1 .170 0.0087%
 


Upcoming Meetings

Anatrace is sponsoring three meetings this July. The 16th Annual International Conference on the Crystallization of Biological Macromolecules (ICCBM) takes place from July 2 – 7, 2016 in Prague, Czech Republic. Edward Pryor, Ph.D. will be giving a talk about the importance of detergent selection when working with membrane proteins during session S1 on July 3rd, and Anatrace will have a booth in the exhibit hall as well (#13). We’re also sponsoring the FASEB meeting on Biophysics of Membranes from July 10-15 in Snowmass, CO. Later in July, we will be attending the 66th Annual American Crystallographic Association (ACA) and will be at booth #34. Stay up to date on all of the conferences Anatrace is attending by visiting out Events Calendar.
 

Errata

In our newsletter last month, we featured two new exciting structures of the glucose transporters GLUT1 and GLUT3. We mistakenly overlooked another important study from the lab of Robert Stroud describing the structures of human GLUT1 cocrystalized with inhibitors(5). We have revised last month’s newsletter to include this work.

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