biostudies-literatureUnknown10(46)Alker KPEG detergents are important tools in the biophysical characterization of membrane protein whose utility is often limited by their intrinsic denaturing properties. This work addresses the question of whether changing the linker between PEG headgroup and nonpolar tail can modulate the denaturing properties of these detergents. To address this question, herein, we introduce the modular architecture of PEG550 detergents and explore its utility for protein purification from membranes and detergent exchange. Our results indicate that PEG550 detergents cannot efficiently solubilize proteins from lysed bacterial membranes. Varying the linker cannot eliminate the denaturing properties that PEG550 detergents can have on a protein during extraction and affinity purification. Interestingly, we find tACS omega56670-56679https://www.ebi.ac.uk/biostudies/studies/S-EPMC12658807biostudies-literatureDrop Dilution Enables the Use of PEG-Derived Detergents for Membrane Protein Purification.PMC12658807Linser RSingh AKVinodakrishnan AKAlker KSingh RSingh SUrner LHLindemann FfalseDrop Dilution Enables the Use of PEG-Derived Detergents for Membrane Protein Purification.PEG detergents are important tools in the biophysical characterization of membrane protein whose utility is often limited by their intrinsic denaturing properties. This work addresses the question of whether changing the linker between PEG headgroup and nonpolar tail can modulate the denaturing properties of these detergents. To address this question, herein, we introduce the modular architecture of PEG550 detergents and explore its utility for protein purification from membranes and detergent exchange. Our results indicate that PEG550 detergents cannot efficiently solubilize proteins from lysed bacterial membranes. Varying the linker cannot eliminate the denaturing properties that PEG550 detergents can have on a protein during extraction and affinity purification. Interestingly, we find t2025-01-01T00:00:00Z2025 Nov2026-06-05T21:20:23.225Z2026-05-22T03:08:53.956ZS-EPMC126588074132250610.1021/acsomega.5c09173