10.07.2015 Views

Proceedings book download - 5Z.com

Proceedings book download - 5Z.com

Proceedings book download - 5Z.com

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

Table 1. Physicochemical properties of the synthesized analoguesCodeAnaloguesHPLCt R (min)R fATLC αR fBGD1S Tyr-Arg-c(Cys-Asp-Pro-Cys)-CONH 210.25 0.21 0.18GD2S Tyr-Arg-c(Cys-Asp-Pro-Cys)-OH 8.24 0.12 0.09GD3S Sal-Arg-c(Cys-Asp-Pro-Cys)-OH 13.38 0.34 0.31GD4S Tyr-Trp-c(Cys-Asp-Pro-Cys)-OH 13.10 0.27 0.28GD5S 2-Nal-Arg-c(Cys-Asp-Pro-Cys)-OH 9.10 0.15 0.17GD6S Sal-Tyr-Arg-c(Cys-Asp-Pro-Cys)-OH 14.22 0.35 0.32GD7S Tyr-D-Arg-c(Cys-Asp-Pro-Cys)-OH 12.90 0.27 0.18GD8S D-Tyr-Arg-c(Cys-Asp-Pro-Cys)-OH 9.11 0.15 0.11GD9S D-Tyr(Et)-Arg-c(Cys-Asp-Pro-Cys)-OH 10.40 0.23 0.14GD10S Thi-Arg-c(Cys-Asp-Pro-Cys)-OH 6.93 0.08 0.08GD11S Tyr-β-Ala-c(Cys-Asp-Pro-Cys)-OH 10.05 0.20 0.14αA) butan-1-ol/water/acetic acid/pyridine (4/1/1/2, v/v); B) butan-1-ol/water/acetic acid(4/5/1 v/v, upper phase)The analogues were studied, under in vivo conditions, for their potentiality as inhibitors ofangiogenesis in chicken embryo chorioallantoic membrane (CAM), as previously described[8]. All the <strong>com</strong>pounds tested in this study, except analogue GD1S and GD3S, had nosignificant activity on angiogenesis in CAM model. In particular, analogue GD3S showedimportant inhibition of angiogenesis at dose-dependent manner (Figure 1A). On the otherhand, peptide GD1S promoted angiogenesis at the higher concentration, but showed slightinhibition at the lower one (Figure 1B). A series of NMR spectra including 1 H, 2D TOCSYand 2D NOESY were recorded on a Varian 600MHz spectrometer for the analogues GD1S,GD2S, GD3S and GD6S. All peptides were dissolved in DMSO-d 6 solvent. The mixingtime for the TOCSY was set to 80ms and for the NOESY 75ms. For the assignment of theproton peaks, standard procedures were followed based on the 2D spectra. NOE constrainshave also provided crucial information regarding the conformation of the peptides insolution. Molecular modelling techniques are currently performed in order to study theconformational properties of the peptides, as well as similarities and differences betweenthem. Finally, experiments are going to be held for the study of these analogues as antiinflammatoryagents.References1. Heckman, D., Kessler, H. Methods in Enzymology 426, 463-495 (2007).2. Avraamides, C.J., Garmcy-Susini, B., Varner, J.A. Nat. Rev. Cancer 8, 604-617 (2008).3. Fields, B.G., Noble, L.R. Int. J. Pept. Prot. Res. 35, 161-214 (1990).4. Barlos, K., Chatzi, O., Gatos, D., Stavropoulos, G. Int. J. Pept. Prot. Res. 37, 513-520 (1991).5. Rink, H. Tetrahedron Lett. 28, 3787-3790 (1987).6. Tam, J.P., Wu, C.R., Liu, W., Zhang, J.W. J. Am. Chem. Soc. 13, 6657-6662 (1991).7. Ellmam, G. Arch. Biochem. Biophys. 82, 70-77 (1959).8. Papadimitriou, E., Polykratis, A., Courty, J., Koolwilk, P., Heroult, M., Katsoris, P. Biochem.Biophys. Res. Commun. 282, 306-313 (2001).445

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!