Abstract
Derivatives of gramicidin S (GS) and its mono- and di-d-cyclohexylalanine (d-Cha) analogs possessing various protecting groups on Orn side chains were prepared. 1H NMR spectra of the unsymmetrically protected analogs [Orn(X)2,Orn(X′)2′,d-Cha4]GS were similar to the composites of the spectra of the symmetrical derivatives [Orn(X)2,2′,d-Cha4,4′]GS and [Orn(X′)2,2′]GS, revealing the proximity of the protecting groups of NδH of Orn residues at the 2 and 2′ positions to the side chains of d-Phe (or d-Cha) residues at the 4 and 4′ positions, respectively. The results indicated the presence of H-bonds between the NδH of Orn and the carbonyl of d-Phe residues in the i → i + 2 sense and not in i → i – 3, which was also supported by the ROESY analysis. The substantially strong H-bonds can explain the observed resistance of the urethane NH of the Orn side chains in the GS derivatives to the N-methylation with CH3I–Ag2O in DMF.
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Stern, A., Gibbons, W.A. and Craig, L.C., Proc. Natl. Acad. Sci. USA, 61 (1968) 734.
Krauss, E.M. and Chan, S.I., J. Am. Chem. Soc., 104 (1982) 6953.
Kawai, M. and Nagai, U., Chem. Lett., (1977) 1397.
Kawai, M., Ohya, M., Fukuta, N., Butsugan, Y. and Saito, K., Bull. Chem. Soc. Jpn., 64 (1991) 35.
Dygert, M., Go, N. and Scheraga, H., Macromolecules, 8 (1975) 750.
Hull, S.E., Karlsson, R., Main, P., Woolfson, M.M. and Dodson, E.J., Nature, 275 (1978) 206.
Ivanov, V.T., Miroshnikov, A.I., Snezhkova, L.G., Ovchinikov, Yu.A., Kulikov, A.V. and Likhtenshtein, G.I., Khim. Prir. Soedin., 9 (1973) 91.
Kawai, M. and Nagai, U., Biopolymers, 17 (1978) 1549.
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Kawai, M., Yamamoto, T., Yamada, K. et al. Stereochemistry of protected ornithine side chains in gramicidin S derivatives and their resistance to N-methylation. Letters in Peptide Science 5, 5–12 (1998). https://doi.org/10.1023/A:1008860509717
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DOI: https://doi.org/10.1023/A:1008860509717