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Fig. 1. Far UV CD spectra in water at 20 µM of mono-lactam analogs (R)-Agl1 and (R)-Agl4 as well as bis-lactam analog (R)-Agl1-(R)-Agl4.The insertion of (R)-Agl motifs into the rytvela sequence influenced the shape of the CDspectra. The CD spectrum of rytvela exhibits a curve shape characteristic of a disorderedstructure [3]. On the other hand, the spectra of the mono Agl analogs ((R)-Agl-1 and (R)-Agl-4) and the bis-Agl analog ((R)-Agl1, (R)-Agl4) showed two maxima around 198 nmand 220 nm, suggesting that these peptides adopt a helical conformation [6]. The betterdefinedmaximum around 200 nm in the spectrum of the bis-Agl analog suggests that theinsertion of the second Agl motif increases helical-like character relative to the mono-Aglanalogs. Overall, the CD characterization has demonstrated that lactam analogs of rytvelaexhibited spectra indicative of helical conformation. Examination of the biological activityof rytvela analogs by lactam scanning has thus been useful for enhancing peptide potencyand for studying conformation-activity requirements.AcknowledgmentsThe authors acknowledge financial support from the Natural Sciences and Engineering ResearchCouncil of Canada (NSERC), the Université de Montréal, the Canadian Institutes of Health Research(CIP-79848) CIHR-Team in GPCR allosteric regulation (CTiGAR), the Fonds Québecois de laRecherché sur la Nature et les Technologies (FQRNT), and equipment made possible from theCanadian Foundation for Innovation. L.R. thanks the Foreign Affairs and International Trade office ofCanada (DFAIT) and the Fonds de la recherché en santé Québec for the post-doctoral researchfellowships.References1. Freidinger, R.M. J. Med. Chem. 46, 5553-5566 (2003) and references within.2. Jamieson, A.G., Boutard, N., Beauregard, K., Bodas, M.S., Ong, H., Quiniou, C., Chemtob, S.,Lubell, W.D. J. Am. Chem. Soc. 131, 7917-7927 (2009).3. Ronga, L., Jamieson, A.G., Beauregard, K., Quiniou, C., Chemtob, S., Lubell, W.D. BiopolymersPeptide Science 94, 183-191 (2010).4. St-Cyr, D.J., Jamieson, A.G., Lubell, W.D. Org. Lett. 12, 1652-1655 (2010).5. Quiniou, C., Przemyslaw, S., Lahaie, I., Hou, X., Brault, S., Beauchamp, M., Leduc, M., Rihakova,L., Joyal, J.-S., Nadeau, S., Heveker, N., Lubell, W.D., Sennlaub, F., Gobeil, Jr. F., Miller, G.,Pshezhtsky, A.V., Chemtob, S. J. Immunol. 180, 6977-6987 (2008).6. Sakurai, K., Chung, S.H., Kahne, D. J. Am. Chem. Soc. 126, 16288-16289 (2004).257

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