Development of highly potent and ective dynorphin A analogues as new medicines

摘要: Dynorphin A (Dyn A), a 17 amino acid peptide H-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln-OH, is potent opioid which interacts preferentially with kappa-opioid receptors. Research in the development of selective and ligands for kappa-receptor important mediating analgesia. Several cyclic disulphide bridge-containing analogues Dyn A, were conformationally constrained putative message or address segment ligand, designed, synthesized assayed. To further investigate conformational topographical requirements residues positions 5 11 these analogues, systematic series A(1-11)-NH2 incorporating sulphydryl-containing acids L- D-Cys D-Pen Cyclic lactam also retained same affinity selectivity (vs. mu- delta-receptors) as parent guinea-pig brain (GPB), but exhibited much lower activity ileum (GPI), thus leading to centrally vs. peripherally peptides. Studies structure-activity relationship provide new insights into importance each residue (and their configurations) high potency good at We report herein progress towards ligands, can act agonists antagonists cell surface receptors that modulate function animal behaviour using various approaches rational ligand-based drug design.