Reducing the Toxicity of Designer Aminoglycosides as Nonsense Mutation Readthrough Agents for Therapeutic Targets.
Basic Information
ID: ALA4831535
Journal: ACS Med Chem Lett
Title: Reducing the Toxicity of Designer Aminoglycosides as Nonsense Mutation Readthrough Agents for Therapeutic Targets.
Authors: Popadynec M, Baradaran-Heravi A, Alford B, Cameron SA, Clinch K, Mason JM, Rendle PM, Zubkova OV, Gan Z, Liu H, Rebollo O, Whitfield DM, Yan F, Roberge M, Powell DA.
Abstract: A significant proportion of genetic disease cases arise from truncation of proteins caused by premature termination codons. In eukaryotic cells some aminoglycosides cause readthrough of premature termination codons during protein translation. Inducing readthrough of these codons can potentially be of therapeutic value in the treatment of numerous genetic diseases. A significant drawback to the repeated use of aminoglycosides as treatments is the lack of balance between their readthrough efficacy and toxicity. The synthesis and biological testing of designer aminoglycoside compounds is documented herein. We disclose the implementation of a strategy to reduce cellular toxicity and maintain readthrough activity of a library of compounds by modification of the overall cationic charge of the aminoglycoside scaffold through ring I modifications.
CiteXplore: 34531957
DOI: 10.1021/acsmedchemlett.1c00349
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