Bioorthogonal Cycloadditions

描述(申请人提供)：本研究方案涉及生理条件下适用于生物分子标记的环加成反应的理解和定量设计。我们将：1.完善的计算方法，用于准确和常规地预测水介质中环加成反应的速率常数；2.完成已知生物正交环加成试剂与给定的环加成反应伙伴之间所有可能的环加成反应的速率常数的计算，但尚未在对其他环加成反应中进行探索。由此得到的二烯和1，3-偶极与一系列烯烃和炔烃的预测速率矩阵将指导发现更多有用的生物正交反应和相互正交反应；3.发展新试剂和正交反应对的通用设计原则；4.构思新的环加成组分并对其进行计算测试，以确定用于生物正交环加成的有前景的反应对。5.计算新设计的荧光探针的荧光波长和量子产率。这一结果将加强对生物过程和疾病状态的监测。

DESCRIPTION (provided by applicant): This research proposal involves the understanding and quantitative design of cycloadditions suitable for biomolecule labeling under physiological conditions. We will: 1. perfect computational methods to be used for accurate and routine predictions of rate constants of cycloadditions in aqueous media; 2. complete the computations of rate constants of all possible cycloadditions between cycloaddends that are known to be bioorthogonal cycloaddition reagents with a given cycloaddition partner but have not been explored in reactivities towards other cycloaddends. The resulting matrix of predicted rates for a series of dienes and 1,3-dipoles with a series of alkenes and alkynes will guide the discovery of additional useful bioorthogonal and mutually orthogonal reactions; 3. develop generalized design principles for new reagents and orthogonal reaction pairs; 4. conceive of new cycloaddition components and test them computationally in order to determine promising reactant pairs for bioorthogonal cycloadditions. 5. Compute fluorescence wavelengths and quantum yields for newly designed fluorogenic probes. The results will enhance the monitoring of biological processes and disease states.