Structure–activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists
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
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- MedChemComm
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MedChemComm 6 (3), 469-476, 2015-01-05
Royal Society of Chemistry
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詳細情報 詳細情報について
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- CRID
- 1050282810790149888
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- NII論文ID
- 120005615647
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- ISSN
- 20402503
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- HANDLE
- 2433/198453
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- CiNii Articles