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Backbone Cyclization of the C‐terminal Part of Substance P. Part 1: The Important Role of the Sulphur in Position 11
Author(s) -
Bitan Gal,
Zeltser Irena,
Byk Gerardo,
Halle David,
Mashriki Yaffa,
Gluhov Evgenia V.,
Sukhotinsky Inna,
Hanani Menachem,
Selinger Zvi,
Gilon Chaim
Publication year - 1996
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.76
Subject(s) - thioether , moiety , chemistry , stereochemistry , side chain , receptor , ring (chemistry) , substance p , cyclic peptide , lactam , peptide , biochemistry , organic chemistry , neuropeptide , polymer
Abstract Novel backbone‐to‐side chain and backbone‐to‐backbone cyclic analogues of substance P (SP) were prepared by solid‐phase synthesis and screened for biological activity. An analogue containing a thioether‐ lactam ring between positions 9 and 11 showed an EC 50 value of 20n M toward the neurokinin 1 (NK‐1) and was inactive toward the NK‐2 and NK‐3 receptors. On the other hand, in a multiple backbone cyclic peptide library of similar analogues, in which the sulphur was excluded from the ring, very low activity was detected. The activity was re‐evaluated and was found to be even lower (EC 50 =0.11 m M ) than the previously published data. These results indicate that the thioether moiety has a crucial role in receptor activation. The results also show tolerance of the NK‐1 receptor, but not NK‐2 or NK‐3, to cyclization of the C‐terminal portion of the SP 6–11 hexapeptide.