Open AccessPhoto-Click-Facilitated Screening Platform for the Development of Hetero-Bivalent Agents with High Potency
Author(s) -
Lingyi Sun,
Yongkang Gai,
Christopher D. McNitt,
Jun Sun,
Xiaohui Zhang,
Wei Xing,
Zhonghan Li,
Vladimir V. Popik,
Dexing Zeng
Publication year - 2020
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.9b03122
Subject(s) - chemistry , click chemistry , potency , virtual screening , combinatorial chemistry , avidity , in vivo , computational biology , in vitro , pharmacology , biochemistry , drug discovery , antibody , microbiology and biotechnology , immunology , biology , medicine
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 agents via streamlining tedious organic synthesis and biological evaluation procedures required by traditional approaches. The high-avidity heterobivalent agents targeting both integrin α v β 3 and urokinase-type plasminogen activator receptors have been developed using this photo-click-facilitated screening platform. The affinity screening results were further validated by traditional in vitro and in vivo evaluation 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.