Small, modular, and monovalent Quantum Dots for single molecule imaging of Notch

描述（由申请人提供）：量子点由于其特殊的光物理特性，具有彻底改变生物成像的潜力。然而，精确控制量子点与其他生物分子之间的界面化学仍然是一个重大的合成挑战，限制了它们在生物学中的广泛应用。制备量子点-生物分子偶联物的常见策略产生的产物具有不明确的价，相对较大的流体动力学尺寸和有限的模块化。为了解决这些问题，从而建立更高性能和更通用的QD成像探针，我们提出了一种创新的合成方法，称为“位阻排除”。该方法使用一种功能化的立体排斥寡核苷酸来包裹QD，从而将反应的范围限制在固定价的物种上。我们建议(i)将量子点单步完全转化为小型（< 12 nm）、模块化、高特异性和单价的生物成像探针；（ii）通过阐明Notch及其加工中间体在活细胞表面的动力学，证明这些探针在具有挑战性的单分子成像应用中的实用性。最终，我们建议将量子点从“特殊用途探针”转变为“多功能和随时可用的生物探针”，供任何学科的科学家使用。

DESCRIPTION (provided by applicant): Quantum dots have the potential to revolutionize biological imaging due to their exceptional photophysical properties. However, precise control over the interfacial chemistry between QDs and other biomolecules remains a significant synthetic challenge limiting their broad application in biology. Common strategies for preparing QD-biomolecule conjugates generate products with poorly defined valency, relatively large hydrodynamic size, and limited modularity. To address these issues and hence to establish higher-performance and more versatile QD imaging probes, we propose an innovative synthetic approach, termed "steric exclusion". The method uses a functionalized steric-exclusion oligonucleotide designed to wrap the QD as it reacts and thereby limits the extent of the reaction to a species of fixed valency. We propose to (i) perform the single-step complete conversion of QDs to bioimaging probes that are small (< 12 nm), modular, highly-specific, and monovalent; and (ii) demonstrate the utility of these probes in a challenging single- molecule imaging application by elucidating the dynamics of Notch and its processing intermediates on the surface of live cells. Ultimately, we propose to transform QDs from "probes for special purposes" to "versatile and ready-to-use bioprobes," accessible to scientists from any discipline.