Repairing faulty genes by aminoglycosides: Development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations
Repairing faulty genes by aminoglycosides: Development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations
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DOI：
10.1016/j.bmc.2010.03.060
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发表时间：
2010-06-01
影响因子：
3.5
通讯作者：
Baasov, Timor
中科院分区：
文献类型：
--
作者：
Nudelman, Igor;Glikin, Dana;Baasov, Timor
设计、合成了氨基糖苷类药物G418的新的假二糖和假三糖衍生物，并在体外和离体系统中检查了它们通读无义突变的能力，沿着毒性试验。发现了两种新的引线结构，NB 74和NB 84，其表现出比庆大霉素显著降低的细胞毒性和上级通读效率。在遗传性疾病囊性纤维化、Duchenne肌营养不良、Usher综合征和Hurler综合征的6种不同的无义DNA结构中证明了新导线的优越性。(C)2010爱思唯尔有限公司保留所有权利。
New pseudo-di- and pseudo-trisaccharide derivatives of the aminoglycoside drug G418 were designed, synthesized and their ability to readthrough nonsense mutations was examined in both in vitro and ex vivo systems, along with the toxicity tests. Two novel lead structures, NB74 and NB84, exhibiting significantly reduced cell toxicity and superior readthrough efficiency than those of gentamicin, were discovered. The superiority of new leads was demonstrated in six different nonsense DNA-constructs underling the genetic diseases cystic fibrosis, Duchenne muscular dystrophy, Usher syndrome and Hurler syndrome. (C) 2010 Elsevier Ltd. All rights reserved.