High-resolution membrane protein structures are essential for understanding the molecular basis of
diverse biological events and important in drug development. Detergents are usually used to extract
these bio-macromolecules from the membranes and maintain them in a soluble and stable state in
aqueous solutions for downstream characterization. However, many eukaryotic membrane proteins
solubilized in conventional detergents tend to undergo structural degradation, necessitating the
development of new amphiphilic agents with enhanced properties. In this study, we designed and
synthesized a novel class of glucoside amphiphiles, designated tandem malonate-based glucosides
(TMGs). A few TMG agents proved effective at both stabilizing a range of membrane proteins and
extracting proteins from the membrane environment. These favourable characteristics, along with
synthetic convenience, indicate that these agents have potential in membrane protein research.