Cyclic analogues of substance P. III. Cyclo-(6V→oligomethylenodiamine ←11) substance P6-11 hexapeptides
F. K. Mutulis, I. E. Mutule, G. H. Maurops, J. Bergmann, N. V. Mishlyakova, G. M. Strazda, E. E. Liepins, J. B. Saulitis, V.D. Grigoryeva, J. J. Balodis, V. I. Tsetlin, J. M. Lazakovich
Institute of Organic Synthesis, Latvian Academy of Sciences, Riga; Central Institute of Molecular Biology, Academy of Sciences of the GDR, Berlin; M. M. Shemyakin Institute of Bioorganic Chemistry, Academy of Sciences of the USSR, Moscow
Abstract: Cyclic analogues of substance P of the formula cyclo-[Glu-Phe-Phe-Gly-Leu-Met-NH(CH2)nNH-], where n=3–10, 12, and open-chain analogues (XVIIIa, b) H-Glu·(NHR)-Phe-Phe-Gly-Leu-Met-NHR, where R= –CH3, –CH2CH2CH3, were synthesized. By NMR spectroscopy it was found that cyclo-compounds with n=3–8 have regularly arranged structures, stabilized by intramolecular hydrogen bonds. Substances of this type showed ≤0.1% of the substance P activity on the guinea pig ileum, but some of them antagonize the natural peptide (for compound with n≤5 IC50=3.2·10-6 M). The open-chain compounds proved to have rather high myotropic activity, viz., 22% (R=–CH3) and 8% (R=–CH2CH2CH3) of the substance P activity.
Russian Journal of Bioorganic Chemistry 1991, 17 (10):1412-1423