論文

査読有り 国際誌
2019年4月11日

Development of a Highly Potent Analogue and a Long-Acting Analogue of Oxytocin for the Treatment of Social Impairment-Like Behaviors.

Journal of medicinal chemistry
  • Wataru Ichinose
  • Stanislav M Cherepanov
  • Anna A Shabalova
  • Shigeru Yokoyama
  • Teruko Yuhi
  • Hiroaki Yamaguchi
  • Ayu Watanabe
  • Yasuhiko Yamamoto
  • Hiroshi Okamoto
  • Shinichi Horike
  • Junpei Terakawa
  • Takiko Daikoku
  • Mizuki Watanabe
  • Nariyasu Mano
  • Haruhiro Higashida
  • Satoshi Shuto
  • 全て表示

62
7
開始ページ
3297
終了ページ
3310
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1021/acs.jmedchem.8b01691

The nonapeptide hormone oxytocin (OT) has pivotal brain roles in social recognition and interaction and is thus a promising therapeutic drug for social deficits. Because of its peptide structure, however, OT is rapidly eliminated from the bloodstream, which decreases its potential therapeutic effects in the brain. We found that newly synthesized OT analogues in which the Pro7 of OT was replaced with N-( p-fluorobenzyl)glycine (2) or N-(3-hydroxypropyl)glycine (5) exhibited highly potent binding affinities for OT receptors and Ca2+ mobilization effects by selectively activating OT receptors over vasopressin receptors in HEK cells, where 2 was identified as a superagonist ( EMax = 131%) for OT receptors. Furthermore, the two OT analogues had a remarkably long-acting effect, up to 16-24 h, on recovery from impaired social behaviors in two strains of CD38 knockout mice that exhibit autism spectrum disorder-like social behavioral deficits, whereas the effect of OT itself rapidly diminished.

リンク情報
DOI
https://doi.org/10.1021/acs.jmedchem.8b01691
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30896946
ID情報
  • DOI : 10.1021/acs.jmedchem.8b01691
  • ISSN : 0022-2623
  • PubMed ID : 30896946

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