Development of Novel Neurokinin 3 Receptor (NK3R) Selective Agonists with Resistance to Proteolytic Degradation
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- 作者：Ryosuke Misu ; Shinya Oishi ; Ai Yamada ; Takashi Yamamura ; Fuko Matsuda ; Koki Yamamoto ; Taro Noguchi ; Hiroaki Ohno ; Hiroaki Okamura ; Satoshi Ohkura ; Nobutaka Fujii
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：October 23, 2014
- 年：2014
- 卷：57
- 期：20
- 页码：8646-8651
- 全文大小：307K
- ISSN：1520-4804
文摘
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.