Molecular Science and Biomedicine Laboratory (MBL), Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China.
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.
Angew Chem Int Ed Engl. 2019 Feb 4;58(6):1621-1625. doi: 10.1002/anie.201809010. Epub 2019 Jan 14.
Regulation of protein activity is essential for revealing the molecular mechanisms of biological processes. DNA and RNA achieve many uniquely efficient functions, such as genetic expression and regulation. The chemical capability to synthesize artificial nucleotides can expand the chemical space of nucleic acid libraries and further increase the functional diversity of nucleic acids. Herein, a versatile method has been developed for modular expansion of the chemical space of nucleic acid libraries, thus enabling the generation of aptamers able to regulate protein activity. Specifically, an aptamer that targets integrin alpha3 was identified and this aptamer can inhibit cell adhesion and migration. Overall, this chemical-design-assisted in vitro selection approach enables the generation of functional nucleic acids for elucidating the molecular basis of biological activities and uncovering a novel basis for the rational design of new protein-inhibitor pharmaceuticals.
蛋白质活性的调节对于揭示生物过程的分子机制至关重要。DNA 和 RNA 实现了许多独特而高效的功能，如遗传表达和调控。人工核苷酸的合成能力可以扩展核酸文库的化学空间，并进一步增加核酸的功能多样性。在此，开发了一种通用的方法来对核酸文库的化学空间进行模块化扩展，从而生成能够调节蛋白质活性的适体。具体来说，鉴定出了针对整合素 α3 的适体，该适体可以抑制细胞黏附和迁移。总的来说，这种化学设计辅助的体外选择方法能够生成功能性核酸，以阐明生物活性的分子基础，并为合理设计新的蛋白抑制剂药物提供新的基础。
