Structural investigations for developing the rapeutics of Altzheimer, prion, and Parkinson's disease

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1. In order to obtain insight how to find out oligqpeptides from the amino acid sequences of A β, PrP, and NAG, oligopeptidemediated helix stabilization of Na channel related peptides has been studied. It was found that oligopeptides should involve hydrophobic amino acids and should be interposed by such polar amino acids as lysine for stabilizing α-helices of the model peptides2. By designing various kinds of oligopeptides from the amino acid sequence of A β, interactions between oligopeptides and Aβ have been studied. Among the oligopeptides studied, only Ac-ELVFFAKK-NH_2 was found to increase β-sheet content and accelerate amyloid fibril formation3. I have selected PrP(129-154) and PrP(192-213) from PrP and studied interactions with the oligopeptides designed from those peptides. Ac-EFGNK-NH_2 and Ac-EYYEK-NH_2 stabilized α-helices of PrP(129-154), but every oligopeptides studied destabilized α-helix of PrP(192-213)4. The peptide Ac-ETVK-NH_2 increased the β-sheet content of NAG in water and accelerated amyloid fibril formation5. If an oligopeptide involves a fragment of amyloidogenic proteins and destabilizes their α-helices, the peptide could be a trigger to initiate amyloid diseases