Backbone Cyclization of the C-terminal Part of Substance P. Part 1: The Important Role of the Sulphur in Position 11

✍ Scribed by Gal Bitan; Irena Zeltser; Gerardo Byk; David Halle; Yaffa Mashriki; Evgenia V. Gluhov; Inna Sukhotinsky; Menachem Hanani; Zvi Selinger; Chaim Gilon

• Book ID: 105360582
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 717 KB
• Volume: 2
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.76

✦ Synopsis

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 thioetherlactam ring between positions 9 and 11 showed an EC50 value of 20 nM 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.