Rationalizing the Optimization of Detergents for Membrane Protein Purification

Membrane protein purification by means of detergents is key to isolating membrane-bound therapeutic targets. The role of the detergent structure in this process, however, is not well understood. Detergents are optimized empirically, leading to failed preparations, and thereby raising costs. Here we evaluate the utility of the hydrophilic-lipophilic balance (HLB) concept, which was introduced by Griffin in 1949, for guiding the optimization of the hydrophobic tail in first-generation, dendritic oligoglycerol detergents ([G1] OGDs). Our findings deliver qualitative HLB guidelines for rationalizing the optimization of detergents. Moreover, [G1] OGDs exhibit strongly delipidating properties, regardless of the structure of the hydrophobic tail, which delivers a methodological enabling step for investigating binding strengths of endogenous lipids and their role for membrane protein oligomerization. Our findings will facilitate the analysis of challenging drug targets in the future.

Automated summary

Membrane protein purification is crucial for isolating therapeutic targets. However, the role of detergent structure in this process is not well understood, leading to failed preparations and increased costs. This study evaluates the use of hydrophilic-lipophilic balance (HLB) concept to optimize dendritic oligoglycerol detergents. The findings provide qualitative HLB guidelines and enable investigation of lipid binding strengths and protein oligomerization.