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NMR-analysis allowed full structural characterization of the cyclic products. In addition tosignals from the assigned peptide amino acids signals were observed corresponding to thearomatic protons of the triazoles. Furthermore, NOESY-experiments revealed NOEs acrossthese triazole bridges The NOEs allowed the determination of the spatial structure of themajor isomer as a ribbon-like -hairpin conformation and of the minor isomer as theglobular product with the wrong triazole connectivity.Lowest energy structures of both conformations were obtained by MD-calculationsbased on the NOEs. A comparison of the ribbon-like structure with that of the originalpeptides showed a high degree of similarity. Thereby, the triazole analogs perfectly mimicthe natural -hairpin fold of the backbone. Furthermore, almost all side chains werecorrectly positioned in analogy to the wild type peptides.Encouraged by these results, the biological activity of the tachyplesin-I analogs wasevaluated in an antimicrobial assay. Several bacteria strains (E.coli, Staphylococcusepidermis, Salmonella typhimurium, Bacillus subtilis) were grown with increased peptideconcentrations and the minimal inhibitory concentrations (MIC) were determined. Thelinear and the globular peptides showed no activity, while the cyclic -hairpin peptidessignificantly inhibited the bacterial growth. Remarkably, the triazole analogs performedsimilar or even better than the wild type tachyplesin.The presented method of mimicking disulfide bonds by triazoles can be consideredwhenever orthogonality and higher stability is requested. The click chemistry approachopens a convenient route to achieve those triazole bridged analogs. The created peptideanalogs show a high degree of structural similarity which is also reflected in relatedbiological activity.AcknowledgmentsThe German Research Foundation (DFG) has supported (KHN) the present work.References1. Bondebjerg, J., Grunnet, M., Jespersen, T., Meldal, M. ChemBioChem 4, 186-194 (2003).2. Hargittai, B., Sole, N.A., Groebe, D.R., Abramson, S.N., Barany, G. J. Med. Chem. 43, 4787-4792(2000).3. Stymiest, J.L., Mitchell, B.F., Wong, S., Vederas, J.C. Org. Lett. 5, 47-49 (2003).4. Muttenthaler, M., et al. J. Am. Chem. Soc. 132, 3514-3522 (2010).5. Tornoe, C.W., Meldal, M. Peptides, The wave of the future (Proceedings of the 17 th AmericanPeptide Symposium, San Diego), Springer 263-264 (2001); Meldal, M., Tornoe, C.W. ChemicalReviews 108, 2952-3015 (2008).6. Chen, J., et al. Cancer Res. 65, 4614-4622 (2005); T. Nakamura, H. Furunaka, T. Miyata, F.Tokunaga, T. Muta, S. Iwanaga, M. Niwa, T. Takao, Y. Shimonishi, J. Biol. Chem. 263, 16709-16713 (1988).7. Brust, A., et al. J. Med. Chem. 52, 6991-7002 (2009).147