Photo-Click-Facilitated Screening Platform for the Development of Hetero-Bivalent Agents with High Potency.
Photo-Click-Facilitated Screening Platform for the Development of Hetero-Bivalent Agents with High Potency.
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用于开发高效异二价药物的照片点击促进筛选平台。
DOI：
10.1021/acs.joc.9b03122
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Zeng,Dexing
中科院分区：
文献类型：
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作者：
Sun,Lingyi;Gai,Yongkang;McNitt,ChristopherD;Sun,Jun;Zhang,Xiaohui;Xing,Wei;Li,Zhonghan;Popik,VladimirV;Zeng,Dexing
一种新的基于光点击的平台已经被开发用于异二价试剂的快速筛选和亲和力优化。这种方法允许通过简化传统方法所需的繁琐的有机合成和生物学评价程序来有效地选择高亲和力的双重受体靶向剂。利用该筛选平台，同时靶向整合素αvβ 3和尿激酶型纤溶酶原激活剂受体的高亲合力异二价药物已被开发出来。用传统的体外和体内评价技术进一步验证了亲和筛选结果，证实了该方法的可靠性。本报告中讨论的筛选平台的方便性、快速性、通用性和稳健性可以极大地促进用于研究和/或临床应用的新的异二价剂的开发。
A novel photo-click-based platform has been developed for rapid screening and affinity optimization of heterobivalent agents. This method allows for the efficient selection of high-affinity dual receptor-targeting agentsviastreamlining tedious organic synthesis and biological evaluation procedures required by traditional approaches. The high-avidity heterobivalent agents targeting both integrin αvβ3and urokinase-type plasminogen activator receptors have been developed using this photo-click-facilitated screening platform. The affinity screening results were further validated by traditionalin vitroandin vivoevaluation techniques, reaffirming the reliability of the method. The convenience, rapidity, universality, and robustness of the screening platform, discussed in this report, can greatly facilitate the development of new heterobivalent agents for research and/or clinical applications.