Sanders 9513357 Membrane proteins reside in the thin sheaths which encapsulate cells and subcellular compartments throughout all biological systems. These proteins represent an important class of biological molecules for which three-dimensional pictorial or "structural" information on the molecular level has been very difficult to obtain. In principle, a physical technique known as "oriented sample nuclear magnetic resonance" (OSNMR) is capable of yielding experimental data which can lead directly to the structures of membrane proteins in a membrane-like environment. However, one of the limitations of current OSNMR technique is the lack of an ideal method for uniformly orienting membrane proteins so that all of the proteins in a sample are lined up in the same direction. The work of this project will seek to overcome this limitation by carrying out the rational design of a new class of membrane-mimicking "model membranes" in which purified membrane proteins can be solubilized and oriented for OSNMR studies. The novel model membrane system which is the goal of this proposal must simultaneously satisfy four criteria: (i) Water must be the solvent. (ii) The liquid crystalline assemblies must be soluble, micelle-like discoidal bilayered particles ("bicelles"). (iii) The bicelles must exhibit nematic order under the influence of a strong magnetic field such that their bilayer normals align in the direction of the applied field. (iv) The liquid crystalline system must not denature membrane proteins solubilized in the novel media. %%% Various considerations predict that these goals will be met by liquid crystals involving a novel series of detergent-like molecules: the "PF-DAPA" surfactants. These compounds will be synthesized via amide condensation of long chain perfluorinated carboxylic acids with the 3-amino group of 2,3 diaminopropionic acid. Their liquid crystalline properties will be characterized using nuclear magnetic resonance. Compositions which satisfy criteria i-iii above will be tested for their ability to solubilize and magnetically orient membrane proteins in native-like conformational states. ***
