Bioorthogonal Cycloadditions

描述（由申请人提供）：本研究计划涉及在生理条件下适合生物分子标记的环添加物的理解和定量设计。我们将：1；完善的计算方法用于准确和常规预测环加成在水介质中的速率常数；2. 完成所有可能的环加成之间的速率常数的计算，已知的生物正交环加成试剂与给定的环加成伙伴，但尚未探索对其他环加成的反应性。所得到的一系列二烯和1,3偶极子与一系列烯烃和炔的反应速率预测矩阵将指导发现更多有用的生物正交和相互正交反应；3. 开发新试剂和正交反应对的通用设计原则；4. 设想新的环加成组分，并对其进行计算测试，以确定有希望的生物正交环加成的反应物对。5. 计算新设计的荧光探针的荧光波长和量子产率。研究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.