n-Dodecyl-β-D-maltoside (DDM): Structure, Properties, and Applications as a Non-ionic Surfactant

What is DDM?

n-Dodecyl-β-D-maltoside (DDM)—also called lauryl maltoside—is a non-ionic alkyl maltoside:

A C12 hydrophobe (dodecyl) glycosidically linked to the disaccharide maltose. It is widely used to extract, solubilize, and stabilize membrane proteins under mild, non-denaturing conditions, and is among the most commonly used detergents in structural biology workflows.

DDM Provided by Aladdin D100662 ≥98%; N475300 Ultra pure ≥98%

Identity & Physicochemical properties that matter in practice

Why DDM is popular

Strengths

· Protein-friendly: Non-ionic sugar headgroup tends to preserve native fold and activity for many membrane proteins. DDM is prominent among detergents used in solved membrane-protein structures.

· Robust micelles: Low CMC + relatively high Nagg → stable micelles that protect hydrophobic surfaces during purification.

· Formulation flexibility: amenable to additive screens and detergent exchange.

And when to rethink it, there are limitations:

Removal can be non-trivial: Low CMC means DDM is hard to dialyze out; prefer adsorptive removal (Bio-Beads SM-2), detergent removal resins, or cyclodextrin extraction, rather than dialysis alone.

Not always the most stabilizing: For some targets, LMNG (lauryl maltose neopentyl glycol L650802) or GDN (glyco-diosgenin G650685 G656374) outperform DDM in long-term stability and cryo-EM sample prep.

Typical working concentrations & buffer patterns

Membrane extraction/solubilization: 

0.1–2% (w/v); ~1% is a common starting point in extraction buffers.

Affinity & SEC buffers: 

Often 0.03–0.1% (maintain above CMC; many protocols allow 0.1–1% through IMAC steps).

GPCR practice:

For class-A GPCRs (e.g., A₂A receptor), DDM is frequently paired with CHS (cholesteryl hemisuccinate) and sometimes CHAPS to better mimic cholesterol-rich membranes and stabilize active states.

Applications of DDM in Membrane Protein Science

1. Extraction of Membrane Proteins

· Strength: DDM’s non-ionic maltoside headgroup and relatively long C12 hydrophobic tail allow it to penetrate membranes without aggressively denaturing proteins.

· Example:

DDM is used to extract G-protein coupled receptors (GPCRs) such as the adenosine A₂A receptor, maintaining ligand binding and conformational flexibility.

Extraction buffers typically use ~1% DDM (≈20 mM), often supplemented with cholesteryl hemisuccinate (CHS) to mimic cholesterol-rich domains.

2. Solubilization of Protein Complexes

· Strength: The relatively large micelles (Nagg ~98, MW ~70 kDa) formed by DDM encapsulate hydrophobic transmembrane regions, keeping proteins soluble and active in aqueous buffers.

· Examples:

Respiratory chain complexes (e.g., cytochrome bc₁, NADH dehydrogenase) have been solubilized in DDM for spectroscopic and structural work.

Transporters and channels (e.g., LacY, aquaporins) are often solubilized in DDM before reconstitution into liposomes or nanodiscs.

3. Stabilization of Membrane Proteins

· Strength: DDM is less harsh than ionic detergents (like SDS) or short-chain non-ionics (like OG), allowing proteins to retain native conformation and function over longer times.

· Examples:

Photosystem I and cytochrome oxidases retain enzymatic activity in DDM.

GPCR–ligand complexes can remain stable for days to weeks in DDM/CHS buffers — long enough for crystallization trials and biophysical assays.

· Hint: Some proteins slowly lose activity in DDM; newer detergents like LMNG (lauryl maltose neopentyl glycol L650802) or GDN (G650685 G656374) sometimes outperform DDM for long-term stability, but DDM remains the standard first-line choice.

4. Structural Biology Workflows

· Strength: DDM is among the most commonly used detergents in structural biology (X-ray crystallography, cryo-EM, NMR), because it balances solubilization strength with mildness.

· Examples:

GPCR structures: Dozens of deposited GPCR crystal and cryo-EM structures list DDM (often with CHS) as the detergent system.

Transporters: Lactose permease (LacY), GLUT1/GLUT3 glucose transporters, and mitochondrial ADP/ATP carriers have been stabilized in DDM.

Photosynthetic complexes: Many cyanobacterial photosystem structures used DDM in extraction buffers.

· Note: In recent years, LMNG (L650802) and GDN(G650685 G656374) have become more prominent in cryo-EM because they can provide higher thermal stability, but DDM is still considered a “benchmark detergent” in screening workflows.

Reference:

1. Sigma-Aldrich / Merck. Product information sheet for n-dodecyl-β-D-maltoside (CAS 69227-93-6). Includes molecular weight, CMC, aggregation number, and usage notes.

2. Anatrace. Technical data for n-dodecyl-β-D-maltoside (DDM). Lists CMC (~0.17 mM), aggregation number (~98), micelle molecular weight (~72 kDa), and solubility notes.

3. Seddon, A. M., Curnow, P., & Booth, P. J. (2004). Membrane proteins, lipids and detergents: not just a soap opera. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1666(1–2), 105–117. Review of membrane protein–detergent interactions; discusses DDM properties and applications.

4. Chae, P. S., Rasmussen, S. G., Rana, R. R., et al. (2010). Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nature Methods, 7(12), 1003–1008. Provides comparative data: DDM vs LMNG for protein stability.

5. Grisshammer, R. (2017). Purification of recombinant G protein-coupled receptors. Methods in Enzymology, 557, 131–156. Describes GPCR extraction with DDM + CHS, with practical concentration ranges.

6. Magnani, F., Shibata, Y., Serrano-Vega, M. J., & Tate, C. G. (2008). Co-evolving stability and conformational homogeneity of the human adenosine A₂A receptor. PNAS, 105(31), 10744–10749. Shows the role of DDM/CHS in stabilizing GPCR conformations.

7. Privé, G. G. (2007). Detergents for the stabilization and crystallization of membrane proteins. Methods, 41(4), 388–397. A widely cited review summarizing CMC, micelle sizes, and comparative detergent usage.

8. Rigaud, J. L., & Lévy, D. (2003). Reconstitution of membrane proteins into liposomes. Methods in Enzymology, 372, 65–86. Discusses detergent removal methods for DDM (Bio-Beads, cyclodextrins).

9. Opekarová, M., & Tanner, W. (2003). Specific lipid requirements of membrane proteins — a putative bottleneck in heterologous expression. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1610(1), 11–22. Discusses how detergent–lipid interactions (including DDM) affect protein activity.

10. Newstead, S., Ferrandon, S., & Iwata, S. (2008). Rationalizing crystallization of membrane proteins in detergents. Science, 321(5886), 365–369. DDM mentioned as a workhorse detergent in early transporter crystallization studies.

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