Assembly of Detergents with Highly Branched Dicarboxylate Clamps for Membrane Protein Studies

The structural knowledge of membrane proteins (MPs) is crucial for the structure-based drug design. The stabilization of MPs during extraction processes is essential for structural and functional maintenance. In this regard, detergents are used to achieve extractions of MPs in their functional form. Based on previous work showing the importance of adjacent dicarboxylate groups for the detergency properties, the synthesis of a new generation of detergents bearing more dicarboxylate groups is reported. The molecular structure of the new generation is characterized by the presence of four chemical entities: a DOTA or NOTA scaffold, three or four pairs of carboxylates, a fatty acid, and PEG chains. The preliminary biochemical evaluation reveals promising features of this novel generation of surfactants for the aqueous extraction of MPs.