The finding that several derivatives of 9-aminoacridine were deacridinylated in the presence of primary aliphatic amines during the solid phase synthesis of acridine-peptide conjugates prompted us to investigate the acridin-9-yl moiety transfer from a relatively low-molecular acridine source to a high-molecular carrier. The hydrophobic polymer was used as a model of hydrophobic core of biologically active proteins. While the alpha-amino group in the peptide was found to play the role of weak acridine acceptor, the epsilon-amino group of lysine appeared to serve as a moderate acceptor of acridine moiety. The covalent modification of the lysine residues side chain in the hydrophobic core of prion protein aggregates could thus explain the discrepancy between the ability of the acridine drug quinacrine to reduce efficiently the incidence of prion protein in cell culture and its weak prion binding affinity.
(c) 2006 Wiley Periodicals, Inc.