Anthracene‐Bridged Detergents for Membrane Protein Studies

Anthracene-bridged detergents (ABDs) are introduced as facial amphiphiles with a rigid, tunable architecture. Evaluations across representative G protein-coupled receptors demonstrate that ABDs offer stabilization performance comparable or superior to conventional detergents. Notably, PP-ABD maintains A_2AAR homogeneity after heat stress and supports electron microscopy analysis, highlighting the potential of ABDs in membrane protein research and detergent design.

Detergents are indispensable for membrane protein (MP) research, yet innovative designs are needed to meet the diverse requirements of MPs. Herein, anthracene-bridged detergents (ABDs) are presented, featuring a curved anthracene-based scaffold with a hydrophobic core and hydrophilic exterior. The modular synthesis of ABDs facilitates a systematic exploration of their structure-property relationships. Evaluation across representative G protein-coupled receptors demonstrates superior or comparable stabilization to conventional detergents. Notably, PP-ABD maintains complete homogeneity of A_2AAR after heat shock and exhibits strong potential for electron microscopy applications. This study establishes ABDs as versatile and effective tools for MP research, offering valuable insights into the rational design of next-generation detergents.

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