Backbone Cyclization of the C‐terminal Part of Substance P. Part 1: The Important Role of the Sulphur in Position 11
- 1 July 1996
- journal article
- research article
- Published by Wiley in Journal of Peptide Science
- Vol. 2 (4) , 261-269
- https://doi.org/10.1002/psc.76
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 EC50 value of 20nM 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 (EC50=0.11 mM) 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 SP6–11 hexapeptide.Keywords
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