101. Small peptides mimicking substance P (1-7) and encompassing a C-terminal amide functionality
- Author
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Anja Sandström, Mathias Hallberg, Rebecca Fransson, Gunnar Lindeberg, Fred Nyberg, and Milad Botros
- Subjects
Male ,Peptidomimetic ,Stereochemistry ,Metabolite ,Peptide ,Substance P ,In Vitro Techniques ,Ligands ,Mass Spectrometry ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Radioligand Assay ,Structure-Activity Relationship ,Endocrinology ,Amide ,Structure–activity relationship ,Animals ,Binding site ,Receptor ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,Membranes ,Endocrine and Autonomic Systems ,Molecular Mimicry ,General Medicine ,Amides ,Peptide Fragments ,Rats ,Neurology ,chemistry ,Biochemistry ,Spinal Cord ,Spectrophotometry, Ultraviolet - Abstract
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 SP(1-7). 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 SP(1-7) 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 SP(1-7) 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 SP(1-7) delivers peptides with retained binding activity, although with somewhat lower binding affinities than SP(1-7) and (c) a C-terminal amide group as a replacement for the terminal carboxy group of SP(1-7) and for all of the truncated ligands synthesized affords approximately 5-10-fold improvements of the binding affinities.
- Published
- 2007