TY - JOUR
T1 - Photo-Click-Facilitated Screening Platform for the Development of Hetero-Bivalent Agents with High Potency
AU - Sun, Lingyi
AU - Gai, Yongkang
AU - McNitt, Christopher D.
AU - Sun, Jun
AU - Zhang, Xiaohui
AU - Xing, Wei
AU - Li, Zhonghan
AU - Popik, Vladimir V.
AU - Zeng, Dexing
N1 - Funding Information:
We thank Kathryn Elizabeth Day and Joseph Donald Latoche for their assistance in PET imaging studies. This work was supported by the National Institute of Biomedical Imaging and Bioengineering grants R21-EB017317 and R21-EB020737 and American Cancer Society Research Scholar (no. ACS-RSG-17-004-01-CCE). Preclinical PET/CT imaging was supported in part by P30CA047904 (UPCI CCSG). The development of photo-SPAAC reagents was supported by NSF (CHE-1565646).
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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 αvβ3 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.
AB - 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 αvβ3 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.
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U2 - 10.1021/acs.joc.9b03122
DO - 10.1021/acs.joc.9b03122
M3 - Article
AN - SCOPUS:85085094313
SN - 0022-3263
VL - 85
SP - 5771
EP - 5777
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 9
ER -