Small peptides mimicking substance P (1-7) and encompassing a C-terminal amide functionality

Some of the biological effects demonstrated after administration of substance P (SP) in vivo can indirectly be attributed to the fragmentation of the undecapeptide to its N-terminal bioactive fragment SP1-7. This heptapeptide (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) is a major bioactive metabolite from SP that frequently exerts similar biological effects as the parent peptide but also, in several cases, completely opposite actions. Specific binding sites for the heptapeptide SP1-7 that are separate from the SP preferred NK receptors have been identified. In this study we demonstrate that (a) the C-terminal part of the SP metabolite SP1-7 is Most important for binding as deduced from an Ala scan and that a replacement of Phe(7) for Ala is deleterious, (b) truncation of the N-terminal amino acid residues Of SP1-7 delivers peptides with retained binding activity, although with somewhat lower binding affinities than SP1-7 and (c) a C-terminal amide group as a replacement for the terminal carboxy group Of SP1-7 and for all of the truncated ligands synthesized affords approximately 5-10-fold improvements of the binding affinities. (c) 2007 Elsevier Ltd. All rights reserved.