Proceedings book download - 5Z.com

Fig. 1. The 50 last conformations of both analogues obtained using MD with TAV.RMSD=0.136 and 0.147 Å for Ca of the cyclic part of Aca[cis-Apc 2 ,Val 4 ]AVP (I) and[Nmp 2 ,D-Arg 8 ]VP (II), respectively.for analogue I and II, respectively, were calculated. The differences arise from differentorientation of the Phe 3 side chain.The addition of 1-adamantanecarboxylic acid (Aca) to the N-terminus andreplacement of the polar Gln residue with hydrophobic Val one enhanced the hydrophobicproperties of analogue I. Consequently, peptide I strongly interacts with the hydrophobicpart of the DPC micelle, which is particularly evident in its N-terminus. The Arg 8 sidechain of analogue I shows the tendency to be associated with negatively charged phosphategroups of the DPC micelle and at the same time, it is located near the hydrophobic part ofthe micelle. In turn, the change of Arg 8 configuration from L to D alters the side chainorientation. Consequently, the D-Arg 8 side chain of analogue II is exposed to the aqueousphase.In summary, the specific orientation of the side chains at positions 2 and 3 is importantfor antagonistic properties. The conformation or/and orientation of the Arg side chainseems to be crucial for interactions with V 1a receptors.AcknowledgmentsThis work was supported by the Polish Scientific Research Committee Grant No. N N204 181736grant and the University of Gdańsk, DS. 8453-4-0169-0. The calculations were carried out in theAcademic Computer Centre (TASK) in Gdańsk, Poland.References1. Schwayzer, R.J. Mol. Recog. 8, 3-8 (1995).2. Toniolo, C., Benedetti, E. Macromolecules 24, 4004-4009 (1994).3. Paul, P.K.C., Sukumar, M., Bardi, R., Piazzesi, A.M., Valle, G., Toniolo, C., Balaram, P. J. Am.Chem. Soc. 108, 6363-6370 (1986).4. Paradisi, M., Torrini, I., Zecchini, G.P., Luente, G., Gauvuzzo, E., Mazza, F., Pochetti, G.Tetrahedron 51, 2379-2386 (1995).5. Wiliamson, M.P. Biochem J. 297, 249-260 (1994).6. Case, D.A., Darden, T.A., Cheatham, III T.E., Simmerling, C.L., Wang, J., Duke, R.E., Luo, R.,Walker, R.C, Zhang, W., Merz, K.M., Roberts, B., Wang, B., Hayik, S., Roitberg, A., Seabra, G.,Kolossváry, I., Wong, K.F., Paesani, F., Vanicek, J., Wu, X., Brozell, S.R., Steinbrecher, T.,Gohlke, H., Cai, Q., Ye, X., Wang, J., Hsieh, M.J., Cui, G., Roe, D.R., Mathews, D.H., Seetin,M.G., Sagui, C., Babin, V., Luchko, T., Gusarov, S., Kovalenko, A., Kollman, P.A. AMBER 11,University of California, San Francisco, 2010.7. Rodziewicz-Motowidło, S., Sikorska, E., Oleszczuk, M., Czaplewski, C. J. Pept. Sci. 14, 85-96,2008.451