Structure-activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonistsElectronic supplementary information (ESI) available. See DOI: 10.1039/c4md00514g

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...

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Main Authors: Misu, Ryosuke, Yamamoto, Koki, Yamada, Ai, Noguchi, Taro, Ohno, Hiroaki, Yamamura, Takashi, Okamura, Hiroaki, Matsuda, Fuko, Ohkura, Satoshi, Oishi, Shinya, Fujii, Nobutaka
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creator Misu, Ryosuke
Yamamoto, Koki
Yamada, Ai
Noguchi, Taro
Ohno, Hiroaki
Yamamura, Takashi
Okamura, Hiroaki
Matsuda, Fuko
Ohkura, Satoshi
Oishi, Shinya
Fujii, Nobutaka
description 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. A potent neurokinin-3 receptor (NK3R) selective agonist with resistance to proteolytic digestion was developed.
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title Structure-activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonistsElectronic supplementary information (ESI) available. See DOI: 10.1039/c4md00514g
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