低分子量小分子可以强烈地结合RNA并影响细胞中的致癌途径
Blessy M Suresh1, Yoshihiro Akahori1, Amirhossein Taghavi1
1Department of Chemistry, The Scripps Research Institute & UF Scripps Biomedical Research, 130 Scripps Way, Jupiter, Florida 33458, United States.
Journal of the American Chemical Society
|November 2, 2022
概括
研究人员开发了一个新的平台和一个大型碎片库, 用小分子准RNA. 鉴定出一种类似药物的片段,能够强烈抑制微RNA-372的处理,从而减少胃癌细胞的表型.
科学领域:
- 生物化学
- 分子生物学
- 医学化学
背景情况:
- 针对小分子,特别是低分子量分子的RNA,在实现足够的亲和力和特异性方面存在重大挑战.
- 开发与RNA的新生物活性相互作用对于治疗进步至关重要.
研究的目的:
- 开发一个能够有效准RNA的小分子识别平台.
- 发现并描述一种能够进行特定RNA调节的新生物活性片段.
主要方法:
- 一个2500个化合物的RNA聚焦小分子碎片集合的构建.
- 使用图书馆对图书馆的选择对抗RNA图书馆来探测超过1280万个RNA片段的相互作用.
- 在人类转录组中挖掘相互作用数据以识别类似药物的碎片.
主要成果:
- 一个具有强大和特定针对microRNA-372头前体的药物样片段的识别.
- 在胃癌细胞中抑制微RNA处理和缓解瘤原型.
- 片段的有利性质的表征:300±130nM亲和度,273Da分子量,QED分数为0.8.
结论:
- 一种低分子量,类似碎片的化合物可以特异性强地调节RNA标.
- 开发的平台可以发现新的RNA向生物活性分子.
- 这种方法有望开发针对涉及特定RNA点的疾病的新疗法.
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