N-Dodecyl-B-D-maltoside (DDM)

N-Dodecyl-B-D-Maltoside, or DDM, is a maltoside based non-ionic detergent with a hydrophilic maltose head and a hydrophobic long chain alkyl tail. It is considered a gentle detergent that is more efficient than other detergents, such as CHAPS or NP-40. It has a comparatively low critical micelle concentration (CMC) of 0.17mM compared to the other maltoside based detergents.The primary attribute of DDM is its capability to extract hydrophobic proteins while maintaining the solution-phase protein conformation. DDM also allows the protein to be reformed following denaturation. Most membrane-bound proteins are α-helix bundles, which are less robust to changes in their cellular environment. DDM offers a detergent capable of preserving these proteins. This is in contrast to other, harsher ionic detergents that destabilize and permanently denature α-helical membrane-bound proteins. DDM has been used to solubilize the multidrug-transporter protein, EmrE, as well as the nucleoside-specific porin protein, Tsx.DDM has also been shown in several cases to facilitate a high degree of reactivation of previously denatured enzymes, possibly due to weak bonding between DDM and intermediate conformational isomers.Common Applications: (Click each for more information) Solubilization of Membrane Proteins for Structural BiologyPurpose: To extract and stabilize membrane proteins in a functional form for crystallography or cryo-EM studies.How It Works: DDM is a mild nonionic detergent that disrupts lipid bilayers while preserving protein conformation and activity. Its long alkyl chain and maltoside headgroup provide a stable micelle environment ideal for protein solubilization.Applications: Used to isolate GPCRs, ion channels, and transporters for X-ray crystallography or cryo-electron microscopy.Carpenter, E. P., Beis, K., Cameron, A. D., & Iwata, S. (2008) . Overcoming the challenges of membrane protein crystallography.Curr Opin Struct Biol, 18 (5), 581–586. doi:10.1016/j.sbi.2008.07.001Reconstitution of Membrane Proteins into Lipid Bilayers or NanodiscsPurpose: To incorporate purified membrane proteins into artificial lipid systems for functional studies.How It Works: DDM-solubilized proteins are transferred into liposomes or nanodiscs by removing detergent via dialysis or absorbents, recreating a native-like lipid environment.Applications: Used in transport assays, electrophysiology, or ligand-binding studies.Denisov, I. G., Grinkova, Y. V., Lazarides, A. A., & Sligar, S. G. (2004) . Directed self-assembly of monodisperse phospholipid bilayer nanodiscs with controlled size.PNAS, 101 (11), 3890–3895. doi:10.1073/pnas.0400046101Detergent Screening in Membrane Protein OptimizationPurpose: To identify the best detergents for expression, solubilization, and downstream structural analysis of target proteins.How It Works: DDM is often included in detergent screening panels due to its broad success in stabilizing diverse membrane proteins.Applications: Initial solubilization screens, comparative stability trials, and expression testing.Privé, G. G. (2007) . Detergents for the stabilization and crystallization of membrane proteins.Methods, 41 (4), 388–397. doi:10.1016/j.ymeth.2007.01.007Key Benefits:Gentle and effective membrane solubilization:Preserves native protein function and structure.Forms stable protein–detergent micelles:Minimizes aggregation and supports purification and structural studies.Low absorbance background:Reduces interference in UV-based protein quantification and optical assays.Established standard in structural biology:Extensively used for crystallography and cryo-EM sample preparation of membrane proteins.Compatible with reconstitution and assay systems:Enables functional analysis in native-like environments.