title: Selective agonists of tachykinin binding sites.
abstract: Three types of binding sites for the mammalian tachykinins, ie Substance P (SP) Neurokinin A (NKA) and Neurokinin B (NKB), have been found in both the central and peripheral nervous systems. Substance P binds to the NK-1 subclass of binding site while NKA and NKB are less selective endogenous ligands, which preferentially interact with the NK-2 and NK-3 subclasses of binding sites, respectively. Complementary strategies, including 3-dimensional structure analysis by NMR spectroscopy and structure-activity relationship led to the design of selective agonists of these binding sites. [Pro9] SP, [Pro10] SP and the cyclic analogues [Cys3,6, Tyr8, Pro9] SP and [Cys3,6, Tyr8, Pro10] SP are selective NK-1 agonists. [Lys5] NKA(4-10) is a water soluble NK-2 potent agonist. Finally, [Pro7] NKB, which completely discriminates NK-2 and NK-3 binding sites, is a water-soluble NK-3 selective agonist.
authors.affiliation: Laboratoire de Chimie Organique Biologique, CNRS UA 493, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Lavielle
authors.forename: G
authors.initials: G
authors.lastname: Chassaing
authors.forename: D
authors.initials: D
authors.lastname: Loeuillet
authors.forename: O
authors.initials: O
authors.lastname: Convert
authors.forename: Y
authors.initials: Y
authors.lastname: Torrens
authors.forename: J C
authors.initials: JC
authors.lastname: Beaujouan
authors.forename: M
authors.initials: M
authors.lastname: Saffroy
authors.forename: F
authors.initials: F
authors.lastname: Petitet
authors.forename: L
authors.initials: L
authors.lastname: Bergström
authors.forename: J
authors.initials: J
authors.lastname: Glowinski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008969:Molecular Sequence Data; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D018039:Receptors, Tachykinin; D015320:Tachykinins / Q000378:metabolism*
chemical_list: D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins