Hydrophobic variations of N-oxide amphiphiles for membrane protein manipulation: importance of non-hydrocarbon groups in the hydrophobic portion.

Amphipathic agents called detergents serve as membrane-mimetic systems to maintain the native structures of membrane proteins during their manipulation. However, membrane proteins solubilized in conventional detergents tend to undergo denaturation and aggregation, necessitating the development of novel amphipathic agents with enhanced properties. Here we describe several new amphiphiles that contain an N-oxide group as the hydrophilic portion. The new amphiphiles have been evaluated for the ability to solubilize and stabilize a fragile multi-subunit assembly from biological membranes. We found that cholate-based agents were promising in supporting retention of the native protein quaternary structure, while deoxycholate-based amphiphiles were highly efficient in extracting/solubilizing the intact superassembly from the native membrane. Monitoring superassembly solubilization and stabilization as a function of variation in amphiphile structure led us to propose that a non-hydrocarbon moiety such as an amide, ether, or a hydroxy group present in the lipophilic regions can manifest distinctive effects in the context of membrane protein manipulation.
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