Proceedings book download - 5Z.com

B)Glp-His-Trp-Lys(Ac)-His-Asp-Trp-Lys-Pro-Gly-NH 2N-O-CH 2 -CO-OOHOHCH 3 O O OHONH 2A)Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH 2Ac-Cys-OS(CH 2 ) 5NOOHPhe-Lys-NOHOOOONHOHOHOOOHOOMeOOHCH 3C)Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH 2OOHN-O-CH 2 -CO--CO-CH 2 -O-NHOOOHHOCH 3 O O OH ONH 2H 2NOHOOOCH 3OOHCH 3HOH 3 COFig. 1. Structure representation of Daunorubicin – GnRH-III bioconjugates.Table 1. In vitro long term antitumor activity of daunorubicin-GnRH-III bioconjugates(IC 50 values determined by MTT assay (μM))Compounds MCF-7 HT-29Glp-His-Trp-Ser-His-Asp-Trp-Lys(Dau=Aoa)-Pro-Gly-NH 2 7.2 ± 2.8 14.2 ± 2.4Glp-His-Trp-N-MeSer-His-Asp-Trp-Lys(Dau=Aoa)-Pro-Gly-NH 2 2.0 ± 0.5 9.2 ± 2.4Glp-His-Trp-Lys(Ac)-His-Asp-Trp-Lys(Dau=Aoa)-Pro-Gly-NH 2 1.3 ± 0.3 3.8 ± 0.4Glp-His-Trp-Lys(Dau=Aoa)-His-Asp-Trp-Lys(Dau=Aoa)-Pro-Gly-NH 2 2.1 ± 0.3 4.3 ± 0.5Glp-His-Trp-Ser-His-Asp-Trp-Lys(Ac-Cys[MC-Phe-Lys-PABC-Dau])-Pro-Gly-NH 22.1 ± 0.4 n.d.MCF-7: IC 50 of Dau: 0.1-0.2 μM; HT-29: IC 50 of Dau: 1-3 μM; n.d. not determinedAcknowledgmentsThis work was supported by grants from the Hungarian National Science Fund (OTKA NK 77485), theMinistry of Health (GVOP-3.2.1.-2004-04-0005/3) and University of Konstanz (Zukunftskolleg andAFF).References1. Singh, Y., Palombo, M., Sinko, P.J. Curr. Med. Chem. 15, 1802-1826 (2008).2. Nagy, A., Schally, A.V. Biol. Reprod. 73, 851-859 (2005).3. Mező, G., Manea, M. Exp. Opin. Drug Deliv. 7, 79-96 (2010).4. Lovas, S., Pályi, I., Vincze, B., Horváth, J., Kovács, M., Mező, I., et al. J. Pept. Res. 52, 384-389(1998).5. Kovács, M., Vincze, B., Horváth, J.E., Seprődi, J. Peptides 28, 821-829, (2007).6. Mező, I., Lovas, S., Pályi, I., Vincze, B., Kálnay, A., Turi, G., et al. J. Med. Chem. 40, 3353-3358(1997).7. Mező, G., Czajlik, A., Manea, M., Jakab, A., Farkas, V., Majer, Z., et al. Peptides 28, 806-820(2007).8. Szabó, I., Manea, M., Orbán, E., Csámpai, A., Bősze, S., et al. Bioconjugate Chem. 20, 656-665(2009).525