title: Development of novel neurokinin 3 receptor (NK3R) selective agonists with resistance to proteolytic degradation.
abstract: Neurokinin B (NKB) regulates the release of gonadotropin-releasing hormone (GnRH) via activation of the neurokinin-3 receptor (NK3R). We evaluated the biological stability of NK3R selective agonists to develop novel NK3R agonists to regulate reproductive functions. On the basis of degradation profiles, several peptidomimetic derivatives were designed. The modification of senktide with (E)-alkene dipeptide isostere generated a novel potent NK3R agonist with high stability and prolonged bioactivity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University , Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Misu
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Ai
authors.initials: A
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Fuko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Koki
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Taro
authors.initials: T
authors.lastname: Noguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohkura
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D000818:Animals; D005260:Female; D006041:Goats; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D020128:Inhibitory Concentration 50; D015287:Neurokinin B / Q000031:analogs & derivatives*; D010052:Ovariectomy; D010446:Peptide Fragments / Q000819:agonists* / Q000145:classification / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D055550:Protein Stability; D018042:Receptors, Neurokinin-3 / Q000819:agonists*; D044967:Serum / Q000378:metabolism; D013373:Substance P / Q000819:agonists / Q000031:analogs & derivatives* / Q000145:classification / Q000378:metabolism; D013552:Swine
chemical_list: D010446:Peptide Fragments; D057786:Peptidomimetics; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; D015287:Neurokinin B; D010447:Peptide Hydrolases