Structure-activity relationship study of tachykinin peptides for the development of novel neurokinin-3 receptor selective agonists

详细信息    查看全文

• 作者：Ryosuke Misu ; Taro Noguchi ; Hiroaki Ohno ; Shinya Oishi ; ^{soishi@pharm.kyoto-u.ac.jp} ; Nobutaka Fujii ; ^{nfujii@pharm.kyoto-u.ac.jp}
• 关键词：GnRH ; gonadotropin-releasing hormone ; ARC ; arcuate nucleus ; NK1R ; neurokinin-1 receptor ; NK2R ; neurokinin-2 receptor ; NK3R ; neurokinin-3 receptor ; LH ; luteinizing hormone ; SP ; substance P ; BH-SP ; Bolton&ndash ; Hunter labeled substance P ; NKA ; neurokinin A
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：15 April, 2013
• 年：2013
• 卷：21
• 期：8
• 页码：2413-2417
• 全文大小：469 K

文摘

Neurokinin B (NKB) is a potential regulator of pulsatile gonadotropin-releasing hormone (GnRH) secretion via activation of the neurokinin-3 receptor (NK3R). NKB with the consensus sequence of the tachykinin peptide family also binds to other tachykinin receptors [neurokinin-1 receptor (NK1R) and neurokinin-2 receptor (NK2R)] with low selectivity. In order to identify the structural requirements for the development of novel potent and selective NK3R agonists, a structure-activity relationship (SAR) study of [MePhe⁷]-NKB and other naturally occurring tachykinin peptides was performed. The substitutions to naturally occurring tachykinins with Asp and MePhe improved the receptor binding and agonistic activity for NK3R. The corresponding substitutions to NKB provided an NK3R selective analog.