NOVEL DETERGENTS FOR CRYSTALLIZING MEMBRANE PROTEINS

THE UNDERSTANDING OF PROTEIN FUNCTION IS GREATLY ENHANCED BYTHE AVAILABILITY OF THREE-DIMENSIONAL STRUCTURAL INFORMATIONOBTAINED BY X-RAY CRYSTALLOGRAPHY. THIS IS TRUE FOR MEMBRANE AS WELL AS WATER-SOLUBLE PROTEINS, BUT THE LARGE, WELL-ORDERED THREE-DIMENSIONAL CRYSTALS REQUIRED FOR X-RAY ANALYSES HAVE BEEN DIFFICULT TO PRODUCE IN THE CASE OF MEMBRANE PROTEINS, AS THEY TEND MORE NATURALLY TO FORM TWO-DIMENSIONAL ARRAYS. A FURTHER COMPLICATING FACTOR IN DEALING WITH MEMBRANE PROTEINS IS THE REQUIREMENT FOR DETERGENTS TO SOLUBILIZE ANDSTABILIZE THE NATIVE STRUCTURE. OF ALL THE DETERGENTS AVAILABLE AND TESTED, ONLY TWO (OCTYLGLUCOSIDE AND LDAO) HAVE PROVEN EFFECTIVE FOR GROWING CRYSTALS SUITABLE FOR HIGH-RESOLUTION X-RAY ANALYSIS. ALTHOUGH CRYSTALLIZATION OFMEMBRANE PROTEINS IS MORE OF AN ART THAN A SCIENCE AS YET, IT IS CLEAR THAT THE STRUCTURE AND THE PURITY OF THE DETERGENT ARE CRITICAL FACTORS IN THE PROCESS. THIS PROJECT WILL SYNTHESIZE A HOMOLOGOUS SERIES OF NOVEL SUBSTITUTED GLUCOSIDES AND MALTOSIDES THAT WILL BE PURE, MILD (NONDENATURING), AND HAVE SOMEWHAT RIGID HYDROPHOBIC TAILS. THEY WILL BE EVALUATED FOR THEIR ABILITY TO SOLUBILIZE MEMBRANE PROTEINS IN AN ACTIVE, MONODISPERSE, STABLE FORM THAT MAY BE COMPATIBLE WITH THREE-DIMENSIONAL CRYSTAL GROWTH.