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研究发现,30%人类致病基因突变属无义突变,基因编码区发生的无义突变可致蛋白翻译在无义突变位点提前终止,导致蛋白功能缺失,引起包括遗传病、肿瘤在内的众多疾病。少数化合物具有无义突变通读作用,可诱导全长蛋白翻译而恢复部分功能,是一种前景广阔的潜在治疗药物。筛选新型无义突变通读剂至关重要,这些工作有赖于通读活性检测方法的发展和完善。目前通读剂活性检测方法主要包括两大类型,原理都是基于蛋白截断试验(protein truncation test,PTT)或报告基因系统。本文较全面地回顾了无义突变通读活性检测方法的发展及最新进展,为高通量筛选方法的建立提供参考,从而进一步推动新型通读剂的筛选工作,发现具有临床药物潜力的候选化合物,用以治疗无义突变所致众多疾病。
The study found that 30% of human pathogenic mutations are nonsense mutations, nonsense mutations in the coding region of the gene can cause protein translation in the nonsense mutation site early termination, resulting in loss of protein function, causing genetic diseases, including cancer Many diseases. A small number of compounds with nonsense mutation read-through, can induce full-length protein translation and restore part of the function, is a promising potential therapeutic drug. Screening for novel nonsense mutants is crucial, and these efforts depend on the development and refinement of the pass-through assay. At present, there are two major types of assays for detecting activity of read-through drugs. The principle is based on protein truncation test (PTT) or reporter system. This review provides a comprehensive review of the development and recent advances in the non-pass-through mutagenesis assay, providing a reference for the establishment of high-throughput screening methods and further promoting the screening of novel read-through reagents. The candidate compounds with potential for clinical drug discovery To treat many diseases caused by nonsense mutations.