Discovery of natural products possessing selective eukaryotic readthrough activity: 3-epi-deoxynegamycin and its leucine adduct

Akihiro Taguchi, Keisuke Hamada, Masaya Kotake, Masataka Shiozuka, Hidemasa Nakaminami, Thanigaimalai Pillaiyar, Kentaro Takayama, Fumika Yakushiji, Norihisa Noguchi, Takeo Usui, Ryoichi Matsuda, Yoshio Hayashi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Herein we report the first discovery of natural readthrough products that do not display antimicrobial activity. Two natural negamycins, 3-epi-deoxynegamycin and its leucine adduct, isolated 37 years ago, were found to be potent readthrough agents against nonsense mutations of eukaryotes, but not prokaryotes, without displaying antimicrobial activity. These results suggest that the compounds are valuable leads for the development of readthrough drugs against nonsense-mediated genetic diseases without the potential for contributing to the emergence of drug-resistant bacteria.

Original languageEnglish
Pages (from-to)2233-2237
Number of pages5
JournalChemMedChem
Volume9
Issue number10
DOIs
Publication statusPublished - Oct 1 2014
Externally publishedYes

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Biological Products
Leucine
Inborn Genetic Diseases
Nonsense Codon
Eukaryota
Pharmaceutical Preparations
Bacteria
epi-deoxynegamycin
negamycin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Discovery of natural products possessing selective eukaryotic readthrough activity : 3-epi-deoxynegamycin and its leucine adduct. / Taguchi, Akihiro; Hamada, Keisuke; Kotake, Masaya; Shiozuka, Masataka; Nakaminami, Hidemasa; Pillaiyar, Thanigaimalai; Takayama, Kentaro; Yakushiji, Fumika; Noguchi, Norihisa; Usui, Takeo; Matsuda, Ryoichi; Hayashi, Yoshio.

In: ChemMedChem, Vol. 9, No. 10, 01.10.2014, p. 2233-2237.

Research output: Contribution to journalArticle

Taguchi, A, Hamada, K, Kotake, M, Shiozuka, M, Nakaminami, H, Pillaiyar, T, Takayama, K, Yakushiji, F, Noguchi, N, Usui, T, Matsuda, R & Hayashi, Y 2014, 'Discovery of natural products possessing selective eukaryotic readthrough activity: 3-epi-deoxynegamycin and its leucine adduct', ChemMedChem, vol. 9, no. 10, pp. 2233-2237. https://doi.org/10.1002/cmdc.201402208
Taguchi, Akihiro ; Hamada, Keisuke ; Kotake, Masaya ; Shiozuka, Masataka ; Nakaminami, Hidemasa ; Pillaiyar, Thanigaimalai ; Takayama, Kentaro ; Yakushiji, Fumika ; Noguchi, Norihisa ; Usui, Takeo ; Matsuda, Ryoichi ; Hayashi, Yoshio. / Discovery of natural products possessing selective eukaryotic readthrough activity : 3-epi-deoxynegamycin and its leucine adduct. In: ChemMedChem. 2014 ; Vol. 9, No. 10. pp. 2233-2237.
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