Proceedings book download - 5Z.com

Table 1. Peptides which were reacted with quinacrineCompound Peptide LengthProductsMono- Bis--acridinylated1 H-Asp-Cys-Val-Asn-OH 4 + +2 H-His-Asp-Cys-Val-Asn-OH 5 + +3 Ac-His-Asp-Cys-Val-Asn-OH 5 + -4 H-Glu-Gln-Met-Cys-Ile-Thr-Asn-OH 7 + +5 H-Glu-Gln-Met-Cys-Val-Thr-Asn-OH 7 + +6 QMCVTQYQKESQAYY 15 + +7 H-Cys-MoPrP(179-212)-Cys-OH 368 Mouse PrP 235 a b ba Recombinant mouse prion protein including anchorb Only bisacridinylated products were obtained; both acridine moieties attached to sulfuratom of cysteine residueSince we proved that quinacrine reacts with prion protein free thio groups of both cysteineresidues, we suggest that the most important interaction between quinacrine and prionprotein is not a complexation of quinacrine by prion as was proposed by Vogtherr [5], but itis the covalent interaction – reaction of quinacrine with free thio group of prion protein.Furthermore we suggest that this reaction might be the key factor for prevention of plaqueformation by quinacrine.AcknowledgmentsThe work was supported by the Grant Agency of the Academy of Sciences (A400550702,M200550902, Z40550506) and the Czech Science Foundation (203/07/1517).References1. Prusiner, S.B. PNAS 95, 13363-13383 (1998).2. Doh-Ura, K., Iwaki, T., Caughey, B. J. Virol. 74, 4894-4897 (2000).3. Šebestík, J., Šafařík, M., Stibor, I., Hlaváček, J. Biopolymers 84, 605-614 (2006).4. Wild, F., Young, J.M. J. Chem. Soc. 7261-7274 (1965).5. Vogtherr, M., Grimme, S., Elshorst, B., Jacobs, D.M., Fiebig, K., Griesinger, C., Zahn, R. J. Med.Chem. 46, 3563-3564 (2003).bb85