The focal point of the efforts for the next years will be to apply solid state NMR to peptides from the prion protein to biologically active aggregate states. We will begin with the "beta" form of the mouse 89-143 peptide containing the P101L mutation, which has been found to stimulate disease in transgenic mice. The inactive helical and coil states of the same peptide will be used for comparison to help identify conformational differences that may relate to the activity. We will also investigate the internal deletion peptide sPrP61, which is myrstylated at the C-terminal residue to mimic the GPI anchor. This peptide also forms ordered aggregates, but unlike the P101L peptide becomes protease resistant, analogous to PrPSc. We will try to generate magnetically ordered samples of fibrils of the peptides (analogous to what has been done for fiber diffraction), which would provide more structural information than available in unordered "powder" samples. We will also explore block- labeled peptides (full labeling for a contiguous set of amino acids) for local structure analysis. We will finish ongoing calibrations for using chemical shielding for determination of phi and psi angles and analyze the extent to which x1 affects analysis and/or can be independently determined. If methods for preparing PrPSc in vitro become available we will prepare specifically labeled samples to compare with the peptide models that have been studied.