A method for the facile solid-phase synthesis of gramicidin S and its analogs

Letters in Peptide Science - Tập 3 - Trang 53-60 - 1996
David S. Wishart1, Leslie H. Kondejewski1, Paul D. Semchuk1, Brian D. Sykes1, Robert S. Hodges1
1Protein Engineering Network of Centres of Excellence, Department of Biochemistry, University of Alberta, Edmonton, Canada

Tóm tắt

A simple method is described for the facile synthesis of gramicidin S and six other analogs, using standard solidphase synthetic technology and a single solution-phase cyclization step. The peptides were purified to homogeneity and characterized by plasma desorption time-of-flight mass spectrometry and NMR spectroscopy. Complete 1H NMR assignments for all seven peptides (in aqueous solution) are presented. Unlike previous approaches, the presented method is simple, automatable, rapid (less than three days), high-yielding, requires no side-chain protection during cyclization, and appears to be generally applicable to the preparation of a variety of related head-to-tail cyclic peptides.

Tài liệu tham khảo

Izumiya, N., Kato, T., Aoyaga, H., Waki, M. and Kondo, M., Synthetic Aspects of Biologically Active Cyclic Peptides: Gramicidin S and Tyrocidines, Halsted Press, New York, NY, 1979. Midez, J.A., Hopfer, R.L., Lopez-Bernstein, G. and Mehta, R.T., Antimicrob. Agents Chemother., 33 (1989) 55. Matsushima, S. and Shichi, H., J. Ocul. Pharmacol., 5 (1989) 261. Okamoto, K., Tomita, Y., Yonezawa, H., Hirohita, T., Ogura, R. and Izumiya, N., Oncology, 41 (1984) 43. Legendre, J.Y. and Szoka, F.C., Proc. Natl. Acad. Sci. USA, 90 (1993) 4374. Betzel, C., Rachev, R., Dolashka, P. and Genov, N., Biochim. Biophys. Acta,1161 (1993) 47. Zhou, N.E., Mant, C.T. and Hodges, R.S., Pept. Res., 3 (1990) 8. Piantini, U., Sørensen, O.W. and Ernst, R.R., J. Am. Chem. Soc., 104 (1982) 6800. Kumar, A., Ernst, R.R. and Wüthrich, K., Biochem. Biophys. Res. Commun., 95 (1980) 1. Braunschweiler, L. and Ernst, R.R., J. Magn. Reson., 53 (1983) 521. States, D.J., Haberkorn, R.A. and Ruben, D.J., J. Magn. Reson., 48 (1982) 286. Krauss, E.M. and Chan, S.I., J. Am. Chem. Soc., 104 (1982) 6953. Tamaki, M., Takimoto, M. and Muramatsu, I., Bull. Chem. Soc. Jpn., 61 (1988) 3925. Klostermeyer, H., Chem. Ber., 101 (1968) 2823 Losse, G. and Neubert, K.. Tetrahedron Lett., 15 (1970) 1267. Sato, K., Abe, H., Kato, T. and Izumiya, N., Bull. Chem. Soc. Jpn., 50 (1977) 1999. Aimoto, S., Bull. Chem. Soc. Jpn., 61 (1988) 2220. Osapay, G., Profit, A. and Taylor, J.W., Tetrahedron Lett., 31 (1990) 2161. Mihara, M., Nishino, N., Ogawa, H.I., Izumiya, N. and Fujimoto, T., Bull. Chem. Soc. Jpn., 65 (1992) 228. Tamaki, M., Akabori, S. and Muramatsu, I., Bull. Chem. Soc. Jpn., 64 (1991) 583. Wilmot, D.M. and Thornton, J.M., J. Mol. Biol., 203 (1988) 221.