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

被引：16

作者：

Misu, Ryosuke ^{[1
]}

Oishi, Shinya ^{[1
]}

Yamada, Ai ^{[1
]}

Yamamura, Takashi ^{[2
]}

Matsuda, Fuko ^{[3
]}

Yamamoto, Koki ^{[1
]}

Noguchi, Taro ^{[1
]}

Ohno, Hiroaki ^{[1
]}

Okamura, Hiroaki ^{[2
]}

Ohkura, Satoshi ^{[3
]}

Fujii, Nobutaka ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

[2] Natl Inst Agrobiol Sci, Anim Physiol Res Unit, Tsukuba, Ibaraki 3050901, Japan

[3] Nagoya Univ, Grad Sch Bioagr Sci, Nagoya, Aichi 4648601, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 20期

关键词：

PULSE-GENERATOR ACTIVITY; ARCUATE NUCLEUS; HORMONE SECRETION; SUBSTANCE-P; KISSPEPTIN/NEUROKININ B/DYNORPHIN; KISSPEPTIN NEURONS; DYNORPHIN-A; RAT; IDENTIFICATION; HYPOTHALAMUS;

D O I：

10.1021/jm500771w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：8646 / 8651

页数：6

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