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）：本研究建议涉及对适用于生物分子标记的环境标记的循环决策的理解和定量设计。我们将：1。用于水性介质中环加成速率常数的准确和常规预测的完美计算方法； 2。完成具有给定的Cycloadition伙伴的众所周知是生物异构环载剂试剂之间所有可能的环加成的速率常数计算，但尚未对其他CycloadDends进行重新探索。一系列二烯和1,3-二极管的预测速率与一系列烯烃和炔烃的预测速率将指导发现其他有用的生物态和相互正交反应； 3。为新试剂和正交反应对制定广义设计原理； 4。构思新的环加成组件并在计算上测试它们，以确定有前途的反应物对生物正交环加成。 5。针对新设计​​的荧光探针计算荧光波长和量子产率。结果将增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

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

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

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