Impact of fluorination on membrane-protein stabilization and extraction by lactobionamide detergents.

Abstract

We report the synthesis of a series of detergents with a lactobionamide polar head group and a tail containing four to seven perfluorinated carbon atoms. Critical micellar concentrations (CMCs) were determined using isothermal titration calorimetry (ITC) and surface tension (SFT) measurements, showing a progressive decrease from 27 mM to about 0.2 mM across the series. While the detergent with the longest fluorinated chain exhibited poor water solubility, the other three derivatives were freely soluble. Dynamic light scattering (DLS) measurements indicated an increase in hydrodynamic diameter with chain length, from 5 nm to 17 nm for the soluble derivatives. We evaluated these detergents for extraction and stabilization of two model membrane proteins, the human adenosine A2A receptor (A2AR) and the Bacillus subtilis multidrug resistance ABC transporter BmrA. The perfluorohexyl derivative demonstrated strong solubilization capacity, while the perfluoropentyl derivative was more effective for stabilization. The lack of a clear correlation between fluoroalkyl chain length and solubilizing or stabilizing efficacy highlights the importance of screening diverse detergents for membrane-protein studies.