2015年
Structure-activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists
MEDCHEMCOMM
- 巻
- 6
- 号
- 3
- 開始ページ
- 469
- 終了ページ
- 476
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1039/c4md00514g
- 出版者・発行元
- ROYAL SOC CHEMISTRY
Neurokinin B (NKB) regulates the secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus via activation of the cognate neurokinin-3 receptor (NK3R). The stimulatory effect of NKB and the derivatives on gonadotropin secretion can potentially be used for development of novel regulatory and therapeutic agents for reproductive dysfunctions. Here, we report a comprehensive structure-activity relationship study on the NK3R-selective agonist peptide, senktide. Substitution of the N-terminal succinyl-Asp substructure in senktide with oxalyl-Glu, oxalyl-D-Glu or oxalyl-L-2-aminoadipic acid (Aad) increased receptor binding and NK3R activation. Among these modifications, the oxalyl-D-Glu substructure prevented neutral endopeptidase (NEP) 24.11-mediated degradation, thus providing a novel NK3R agonist peptide with favourable biological and stability properties.
- リンク情報
- ID情報
-
- DOI : 10.1039/c4md00514g
- ISSN : 2040-2503
- eISSN : 2040-2511
- ORCIDのPut Code : 26307009
- Web of Science ID : WOS:000351095400012
- ORCIDで取得されたその他外部ID : a:1:{i:0;a:1:{s:8:"other-id";s:19:"WOS:000351095400012";}}