Small micelles leading to big results.
That all leads to higher standards.

For years, DDM has been the primary detergent used for the solubilization, purification, and crystallization of membrane proteins.  As shown in our February, 2017 newsletter, DDM was used in the solubilization and purification of over 55% of the unique membrane protein structures deposited in 2016. Additionally, since its development in 2010(1), we have also seen the rapid rise of the use of LMNG (two DDM molecules linked by a quaternary carbon) in membrane protein studies, most notably in the GPCR field. 

While useful for crystallization, there are very few examples of the successful use of non-ionic detergents, such as DDM and LMNG, in nuclear magnetic resonance (NMR) studies of membrane proteins. This is most likely due to the large size of DDM (72 kDa)(2) and LMNG (91 kDa)(3) micelles in solution. This desire to find an uncharged detergent for NMR studies of membrane proteins has led to the recent characterization by the laboratory of Chuck Sanders at Vanderbilt University of the alkyl glucoside n-dodecyl-β-melibioside (β-DDMB)(4). This new detergent differs from DDM in that it contains the disaccharide melibiose (D-Gal-α(1→6)-D-Glc) instead of maltose (D-Glc-α(1→4)-D-Glc) as the head group. Compared to DDM, β-DDMB has a slightly higher CMC (0.3 mM; DDM = 0.17 mM), and forms smaller micelles (42 kDa), even though both detergents contain a disaccharide linked to a 12-carbon alkyl tail. Interestingly, unlike DDM, the size of β-DDMB micelles does not change as a factor of detergent concentration, temperature, pH, and ionic strength, showing the utility of this detergent in a wide range of conditions.

The effectiveness of β-DDMB micelles as a medium for NMR was tested with three different membrane proteins: the single pass transmembrane domain of Notch1; the single pass C99 domain of human amyloid precursor protein; and the 4TM human peripheral myelin protein 22.  NMR spectra for each of these three proteins was collected using β-DDMB, and the detergent previously shown to yield the best spectra for these proteins.  In all three cases, β-DDMB was seen to yield NMR spectra of equal or greater quality than the detergents that previously yielded the best spectra. These results are an important step forward for non-ionic detergents, which have been used infrequently for NMR studies of membrane proteins.  Visit the product page for β-DDMB here.

A Variation on a Theme:

The success of DDM and LMNG suggest that the combination of a disaccharide linked to a 12-carbon alkyl tail is important to the solubilization and stabilization of membrane proteins.  In addition to the recent characterization of β-DDMB described here, this observation has led to the recent development and release of other new detergents, such as Dodecyl Trehaloside (DDTre)(5), which replaces the disaccharide maltose with a trehalose, and Mannitol-Based Amphiphiles (MNA)(6), which have two flexible alkyl chains connected to four glucose groups via a mannitol linker.