Misu Ryosuke, Noguchi Taro, Ohno Hiroaki, Oishi Shinya, Fujii Nobutaka
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Bioorg Med Chem. 2013 Apr 15;21(8):2413-2417. doi: 10.1016/j.bmc.2013.01.036. Epub 2013 Feb 1.
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 [MePhe(7)]-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.
神经激肽B（NKB）是通过激活神经激肽3受体（NK3R）对促性腺激素释放激素（GnRH）脉冲式分泌进行潜在调节的物质。具有速激肽肽家族共有序列的NKB也以低选择性与其他速激肽受体[神经激肽1受体（NK1R）和神经激肽2受体（NK2R）]结合。为了确定新型强效和选择性NK3R激动剂开发的结构要求，对[MePhe(7)]-NKB和其他天然存在的速激肽肽进行了构效关系（SAR）研究。用天冬氨酸和甲基苯丙氨酸对天然存在的速激肽进行取代，改善了对NK3R的受体结合和激动活性。对NKB进行相应取代得到了一种NK3R选择性类似物。
