Compounds for selective translational inhibition.

Compounds for selective translational inhibition.
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用于选择性翻译抑制的化合物。

DOI:
10.1016/j.cbpa.2022.102158
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发表时间:
2022
期刊:
Curr Opin Chem Biol.
影响因子:
--
通讯作者:
Shichino Y and Iwasaki S
Shichino Y and Iwasaki S
中科院分区:
--
文献类型:
--
作者:
Zhao T;Chida A;Shichino Y;Choi D;Mizunuma M;Iwasaki S;and Ohya Y;Shichino Y and Iwasaki S

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由于许多人类疾病是由不受欢迎的有害蛋白质的产生引起的,选择性抑制蛋白质合成的化合物应该为药物开发提供一条独特的途径,扩大可药物蛋白质组。尽管研究受翻译抑制剂优先影响的RNA/氨基酸背景存在分析障碍,但核糖体分析技术的应用克服了这一问题。事实上,这项技术揭示了小分子如氯霉素、大环内酯、PF846和螺柱酸盐对翻译抑制的选择性。尽管这些化合物针对一般的翻译机制,但对它们如何激发上下文选择性的分子理解有助于合理的药物设计和治疗目的的发现。
Since many human diseases are caused by the unwelcome production of harmful proteins, compounds that selectively suppress protein synthesis should provide a unique path for drug development, expanding the druggable proteome. Although surveying the RNA/amino acid contexts that are preferentially affected by translation inhibitors has presented an analytic hurdle, the application of a technique termed ribosome profiling overcomes this problem. Indeed, this technique uncovers the selectivity of translation repression by small molecules such as chloramphenicol, macrolides, PF846, and rocaglates. The molecular understanding of how the compounds inspire context selectivity, despite their targeting to general translation machinery, facilitates rational drug design and discovery for therapeutic purposes.
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