Structure–activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists

• Misu, Ryosuke

• Yamamoto, Koki

• Yamada, Ai

• Noguchi, Taro

• Ohno, Hiroaki

• Yamamura, Takashi

• Okamura, Hiroaki

• Matsuda, Fuko

• Ohkura, Satoshi

• 大石, 真也

• Fujii, Nobutaka

抄録

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.

収録刊行物

• MedChemComm

  MedChemComm 6 (3), 469-476, 2015-01-05

  Royal Society of Chemistry

詳細情報

• CRID: 1050282810790149888
• NII論文ID: 120005615647
• ISSN: 20402503
• HANDLE: 2433/198453
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles