Rationalizing the Optimization of Detergents for Membrane Protein Purification

被引:13
|
作者
Urner, Leonhard H. [1 ,3 ]
Junge, Florian [2 ]
Fiorentino, Francesco [3 ,4 ]
El-Baba, Tarick J. [3 ]
Shutin, Denis [3 ]
Noelte, Gideon [2 ]
Haag, Rainer [2 ]
Robinson, Carol V. [3 ]
机构
[1] TU Dortmund Univ, Dept Chem & Chem Biol, Otto Hahn Str 6, D-44227 Dortmund, Germany
[2] Free Univ Berlin, Inst Chem & Biochem, Takustr 3, D-14195 Berlin, Germany
[3] Kavli Inst Nanosci Discovery, South Pk Rd, Oxford OX1 3QU, England
[4] Sapienza Univ Rome, Dept Drug Chem & Technol, Ple A Moro 5, I-00185 Rome, Italy
基金
欧洲研究理事会;
关键词
detergent; HLB; lipid; membrane; protein; MASS-SPECTROMETRY; LIPID-BINDING; SOLUBILIZATION; STABILIZATION; TRANSPORTERS; ANTIBIOTICS; AMPHIPHILES;
D O I
10.1002/chem.202300159
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页数:13
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