Development of Novel Neurokinin 3 Receptor (NK3R) Selective Agonists with Resistance to Proteolytic Degradation

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 profil...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2014-10, Vol.57 (20), p.8646-8651
Hauptverfasser:	Misu, Ryosuke, Oishi, Shinya, Yamada, Ai, Yamamura, Takashi, Matsuda, Fuko, Yamamoto, Koki, Noguchi, Taro, Ohno, Hiroaki, Okamura, Hiroaki, Ohkura, Satoshi, Fujii, Nobutaka
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Female Goats Humans Hypothalamus - metabolism Inhibitory Concentration 50 Neurokinin B - analogs & derivatives Ovariectomy Peptide Fragments - agonists Peptide Fragments - classification Peptide Fragments - metabolism Peptide Hydrolases - metabolism Peptidomimetics - chemistry Peptidomimetics - pharmacology Protein Stability Receptors, Neurokinin-3 - agonists Serum - metabolism Substance P - agonists Substance P - analogs & derivatives Substance P - classification Substance P - metabolism Swine
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm500771w