Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity

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Zeitschriftentitel:	Proceedings of the National Academy of Sciences
Personen und Körperschaften:	Baradaran-Heravi, Alireza, Niesser, Jürgen, Balgi, Aruna D., Choi, Kunho, Zimmerman, Carla, South, Andrew P., Anderson, Hilary J., Strynadka, Natalie C., Bally, Marcel B., Roberge, Michel
In:	Proceedings of the National Academy of Sciences, 114, 2017, 13, S. 3479-3484
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	Proceedings of the National Academy of Sciences
Schlagwörter:	Multidisciplinary

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Zusammenfassung:	<jats:title>Significance</jats:title> <jats:p>The small number of patients for each of the >5,000 rare genetic diseases restricts allocation of resources for developing disease-specific therapeutics. However, for all these diseases about 10% of patients share a common mutation type, nonsense mutations. They introduce a premature termination codon (PTC) that forms truncated proteins. Pharmaceutical gentamicin, a mixture of several related aminoglycosides, is an antibiotic frequently used in humans that shows weak and variable PTC readthrough activity. Using a variety of in vitro and in vivo assays we report that the major gentamicin components lack PTC readthrough activity but that a minor component, gentamicin B1, is responsible for most of the PTC readthrough activity of this drug and has potential to treat patients with nonsense mutations.</jats:p>
Umfang:	3479-3484
ISSN:	1091-6490 0027-8424
DOI:	10.1073/pnas.1620982114