Most of the detergents that are in use today were available 5 or 10 years ago. Maybe the purity has increased over time, but the list of detergents extracted from successfully crystallized membrane proteins really hasn't seen any substantial additions in the past few years. In the previous blog "Applying the 80/20 rule to membrane protein crystallization pre-screening" I showed a list of detergents and referenced statistics that show that with just 8 detergents (dodecyl maltoside, decyl maltoside, nonyl glucoside, octyl glucoside, LDAO, C12E8 C12E9 and undecylmaltoside) about 80% of the membrane protein crystallization 'landscape' is captured. If you're not working on beta barrel proteins you may as well remove the polyoxyethylene ethers and do with six detergents only, three of them being maltosides.
Only rarely new detergents are conceived, synthesized and tested with membrane proteins. Pil Seok Chae, Sam Gellman and others have done just that, and more: they've come up with a great new detergent class. This is their recent paper on their new series of detergents, called MNGs (maltose-neopentyl glycol amphiphiles):
Chae, P., Rasmussen, S., Rana, R., Gotfryd, K., Chandra, R., Goren, M., Kruse, A., Nurva, S., Loland, C., Pierre, Y., Drew, D., Popot, J., Picot, D., Fox, B., Guan, L., Gether, U., Byrne, B., Kobilka, B., & Gellman, S. (2010). Maltose–neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins Nature Methods, 7 (12), 1003-1008 DOI: 10.1038/nmeth.1526
The MNG molecule looks like this:
Figure: Welcome to the detergent family, MNGs: maltose-neopentyl glycol amphiphiles. Reserving a spot in the front row on the detergent shelf in the freezer may be a good idea.
The molecule architecture, with the neopentyl in it center, was deliberately designed to provide a more rigid environment for membrane protein crystallization. Looking at the list of preferred detergents, the choice of maltosides (sic!) as a head group seems to be a non-brainer (this is in retrospect, mind you), but the concept of a quarternary carbon is unique. The successful applications of this new detergent series range from stabilization (activity of beta 2 adrenergic receptor after detergent exchange from DDM), thermostability (of melibiose permease), solubilization (leucine transporter, light harvesting complex and photosynthetic reaction center) and crystallization (cytochrome b6f & b2AR). While an improvement of crystal quality for cytochrome b6f was not seen, the authors mention that MNG-3 aided in improving crystals of agonist bound beta 2 adrenergic receptor.
I raise may glass to Pil Seok and Sam: well done!