Bioorthogonal Cycloadditions

生物正交环加成

• 批准号: 9387446
• 负责人: KENDALL N HOUK
• 金额: $ 27.93万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387446
• 关键词: Alkenes; Alkynes; Biological; Biological Monitoring; Biological Process; Carbohydrates; Cell physiology; Cells; Characteristics; Collaborations; Computer Analysis; Computing Methodologies; Disease; Evolution; Feedback; Fluorescence; Future; Image; Label; Letters; Location; Mechanics; Metabolic; Metabolism; Modeling; Nucleic Acids; Physiological; Positioning Attribute; Proteins; Reaction; Reagent; Reporter; Research Proposals; Series; Sulfhydryl Compounds; Testing; Time; Water; aqueous; biological systems; biomaterial compatibility; cycloaddition; density; design; diene; experimental study; guided inquiry; in vivo; public health relevance; quantum; rapid detection; theories

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.

描述（由申请人提供）：本研究计划涉及对适合生理条件下生物分子标记的环加成的理解和定量设计。我们将： 1. 完善的计算方法，用于准确和常规预测水介质中环加成反应的速率常数； 2. 完成已知为与给定环加成伙伴的生物正交环加成试剂的环加成之间所有可能的环加成反应的速率常数的计算，但尚未探索与其他环加成的反应性。由此产生的一系列二烯和 1,3-偶极子与一系列烯烃和炔烃的预测速率矩阵将指导发现其他有用的生物正交和相互正交反应； 3. 制定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进行计算测试，以确定有希望的生物正交环加成反应物对。 5. 计算新设计的荧光探针的荧光波长和量子产率。结果将加强对生物过程和疾病状态的监测。

项目成果

Origins of halogen effects in bioorthogonal sydnone cycloadditions.

• DOI: 10.1039/c8cc02128g
• 发表时间: 2018-05-15
• 期刊: Chemical communications (Cambridge, England)
• 作者: Tao H ;Liu F ;Zeng R ;Shao Z ;Zou L ;Cao Y ;Murphy JM ;Houk KN ;Liang Y
• 通讯作者: Liang Y

Readily Accessible Ambiphilic Cyclopentadienes for Bioorthogonal Labeling.

• DOI: 10.1021/jacs.8b02978
• 发表时间: 2018-05-23
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Levandowski BJ;Gamache RF;Murphy JM;Houk KN
• 通讯作者: Houk KN

More Than π-π-π Stacking: Contribution of Amide-π and CH-π Interactions to Crotonyllysine Binding by the AF9 YEATS Domain.

• DOI: 10.1021/jacs.0c06568
• 发表时间: 2020-10-07
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Krone MW;Travis CR;Lee GY;Eckvahl HJ;Houk KN;Waters ML
• 通讯作者: Waters ML

Bioorthogonal Cycloadditions: Computational Analysis with the Distortion/Interaction Model and Predictions of Reactivities.

• DOI: 10.1021/acs.accounts.7b00265
• 发表时间: 2017-09-19
• 期刊: Accounts of chemical research
• 影响因子: 18.3
• 作者: Liu F;Liang Y;Houk KN
• 通讯作者: Houk KN

Computational Exploration of Concerted and Zwitterionic Mechanisms of Diels-Alder Reactions between 1,2,3-Triazines and Enamines and Acceleration by Hydrogen-Bonding Solvents.

• DOI: 10.1021/jacs.7b08325
• 发表时间: 2017-12-20
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Yang YF;Yu P;Houk KN
• 通讯作者: Houk KN