手性碳量子点的绿色合成及其对DNA构象和功能的调控研究

The chiral structures of nanomaterials are concerned with their biological effects. Therefore, research on the interaction mechanism between the chiral namomaterials and biomacromolecules is essential for understanding their biological effects and promoting their biological applications. This project focuses on the green synthesis of chiral carbon quantum dots and their regulation for DNA conformation and function. Specifically, 1) heteroatom doped chiral carbon dots will be greenly synthesized via the hydrothermal method by using amino acids as the carbon sources. 2) Combined with molecular dynamic simulations, the chiral recognition of DNA and conformational regulation of the carbon dots on DNA will be studied to elucidate the structure-activity relationships. 3) To further study the effects of the conformational change on expression of DNA, such as the transcription of mRNA and translation of the protein, in vitro transcription and protein synthesis system will be utilized. The relative regulatory mechanisms and the structure-activity relationships of carbon quantum dots and the regulatory effect on DNA will be investigated. The project intends to provide theoretical supports for understanding the biological effects of chiral nanomaterials from the molecular level, and lays a solid foundation for the biological application of nanomaterials.

纳米材料的手性特征对其生物学效应有重要影响。因此，研究手性纳米材料与生物大分子的相互作用和机制，对理解手性纳米材料的生物学效应、推进其生物应用至关重要。本项目拟聚焦手性碳量子点的绿色合成及其与生物大分子DNA的相互作用和机制研究，并探索手性碳量子点对DNA构象和基因功能的调控作用。具体为：1）以手性氨基酸为碳源，通过水热法绿色合成一系列杂原子掺杂的手性碳量子点；2）研究不同构象的DNA分子对碳量子点的手性识别和碳量子点对DNA的构象调控，探索手性碳量子点的理化性质对手性识别和调控作用的影响，阐明构效关系；再结合分子动力学模拟，揭示调控机制；3）利用无细胞转录系统和无细胞蛋白表达系统，研究构象变化对DNA的转录和翻译功能的影响，探索碳量子点对DNA的基因功能调控机制，完善DNA构效关系。本项目从分子水平为理解手性纳米材料的生物学效应提供理论依据，并为纳米材料的生物学应用奠定重要基础。

纳米材料的手性特征对其生物学效应有重要影响。因此，研究手性纳米材料与生物大分子的相互作用和机理，对理解手性纳米材料的生物学效应、推进其生物应用至关重要。本项目以手性半胱氨酸为前体物质制备了手性碳点（L-CDs和D-CDs）与不同杂原子掺杂的碳量子点，探究了手性碳点模拟拓扑异构酶I的活性。D-CDs比L-CDs具有更优异的类酶催化活性，表现出手性依赖性；催化机理研究显示，碳点嵌插DNA双链后，催化氧气产生羟基自由基（•OH），导致DNA磷酸骨架的断裂；分子动力学模拟进一步证明了D-CDs与DNA有更强的亲和力，进而表现出更高的催化活性；无细胞蛋白表达显示碳点能够提高蛋白表达水平，且D-CDs的增强水平要高于L-CDs，该研究对深入理解DNA的拓扑结构在转录翻译等生命过程中的作用提供了重要理论基础。