Development of controlling technology for protein dissociation and aggregation using high pressure.

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Protein aggregation is one of the serious problems for human health and production of recombinant proteins. Purpose of this study is development of controlling technology for protein dissociation and aggregation using high pressure. In this study, we did following four topics. 1. We observed denaturation process of hen lysozyme using high pressure NMR spectroscopy, in which high pressure suppress protein aggregation. We succeed to observe low-lying excited states and unfolding intermediates at equilibrium condition(Kamatari et al., Biophys Chem. 156, 24-30, 2011). 2. We made a high-volume high pressure apparatus and did refolding experiments from inclusion bodies. 3. We made a high pressure apparatus for fluorescence spectroscopy and observed dissociation process of amyloid fibrils. 4. We used chemical compounds to suppress aggregation in addition to high pressure. We found several new anti-prion compounds(Hosokawa-Muto et al., Antimicrob. Agents Chemother., 53, 765-771, 2009). We optimized a anti-prion compound, GN8, and found higher efficiency compound than GN8(Kimura et al., Bioorg Med Chem Lett. 21, 1502-1507, 2011).