Journal
CHEMMEDCHEM
Volume 9, Issue 10, Pages 2233-2237Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201402208
Keywords
(+)-negamycin; natural products; nonsense mutations; peptides; readthrough activity
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Funding
- Japan Society for the Promotion of Science (JSPS), KAKENHI [23390029, 25860092, 25893258]
- Platform for Drug Discovery, Informatics and Structural Life Science
- Intramural Research Grant for Neurological and Psychiatric Disorders on NCNP [23-5]
- Fugaku Trust For Medicinal Research
- Grants-in-Aid for Scientific Research [26102740, 25893258, 25860092] Funding Source: KAKEN
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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.
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