Structure–activity relationship study on polyglutamine binding peptide QBP1

Abstract

Aggregation and deposition of expanded polyglutamine proteins in the brain cause neurodegenerative diseases including Huntington disease. This pathogenic process is suppressed and delayed in the presence of polyglutamine binding peptide 1 (QBP1), which we previously identified as an undecapeptide binding to pathogenic polyglutamine proteins from phage display peptide libraries. In this paper, a structure–activity relationship study on QBP1 was conducted to determine the pharmacophores for inhibition of polyglutamine aggregation. Furthermore, a truncation study identified an octapeptide as the minimum structure for suppressing aggregation of polyglutamine proteins, which is equipotent to the parent undecapeptide QBP1.