Development of a drug for the polyglutamine diseases by molecular design of chemical analogues of the aggregation inhibitor peptide QBP1

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Toward developing a drug for the polyglutamine(polyQ) neurodegenerative diseases by molecular design of chemical analogues of the aggregation inhibitor peptide QBP1, 1) we identified the minimal sequence of QBP1(WKWWPGIF) and five essential residues within QBP1 for its activity. We also found a tight correlation between their aggregation inhibitory activity and polyQ binding affinity. 2) We further showed by NMR analyses that the polyQ stretch does not adopt an ordered structure in the QBP1-polyQ complex.