Design And Synthesis Of Novel Detergent For Membrane Protein Study

Membrane proteins(MPs)are important drug targets.However,compared to soluble proteins,studies of MPs are far behind.There are only 3.5%of the crystal structures for MPs in the protein data bank.MPs are amphipathic molecules which need proper membrane-like system in the manipulation.It is urgent to develop enough and systematic amphiphilic systems for various biophysics studies.Using traditional glycosyl detergents as templates,we introduced azide and terminal alkynyl groups at its hydrophilic and hydrophobic links and prepared synthetic building blocks.Based on click chemistry,we systematically built a combinatorial detergent library.Through high-throughput screening,optimal detergents were obtained for A2a receptor and transporter MsbA.Additionally,we carried out the development of chemically cleavable detergent that can be quickly removed to facilitate the efficient reconstitution of MPs.