Design and Synthesis of the Diazirine-based Clickable Photo-Affinity Probe
Letters in Drug Design & Discovery, 2019, Vol. 16, No. 6 683
inhibitory activity study showed that PAL-1 exhibited
superior selectivities for SMS2 with an IC50 of 0.37 µM
over SMS1. Besides, the PAL-1’s photolysis product in
methanol was conjectured as the self-quenching product
based on the molecular weight test. Moreover, the
photoactivated labeling experiment of PAL-1 with SMS2
was conducted and the labeled complex was identified as a
mono-labeled product through the mass spectrum. Thus, we
believed that PAL-1 would be a chemical tool for probing
the binding sites and the interaction of the small molecule
inhibitors of SMS2. In addition, with this clickable photo-
affinity probe PAL-1, the activity-based protein profiling
(ABPP), the labeling site analysis, and the cell-based photo-
affinity labeling are ongoing in our lab for further
understanding the molecular mechanism of action of small
molecules that bind to SMS2.
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LIST OF ABBREVIATIONS
ABPP
CPE
PAL
PC
=
=
=
=
=
=
Activity-Based Protein Profiling
Ceramide Phosphoethanolamine
Photo-Affinity Labeling
Phosphatidylcholine
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CONSENT FOR PUBLICATION
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[10]
FUNDING
This study was financially supported by the Shanghai
Municipal Committee of Science and Technology (No
17431902300), the program for Shanghai Rising Star (No
15QA1400300), and the Open Grant (2015-2017) of the
State Key Laboratory of Bio-organic and Natural Products
Chemistry, Chinese Academy of Sciences and the National
Science & Technology Major Project “Key New Drug
Creation and Manufacturing Program”, China (No
2018ZX09711002).
[11]
[12]
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CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
Lu Zhou & Deyong Ye conceived and designed the
research; Penghui Wang performed the experimental works
and wrote the manuscript, Zhining Li and Lulu Jiang
participated in the experimental works, analyzed the data and
discussed the results. The authors also gratefully acknowledge
Prof. Youhong Hu and Dr. Wenming Ren from the Shanghai
Institute of Materia Medica, Chinese Academy of Sciences, and
Dr. Chao Peng from the National Center for Protein Science
(Shanghai) for providing the 365 nm UV lamp and the analysis
of mass spectrometry of macromolecules respectively.
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Gao, R.F.; Kinami, S.; Kosaka, T.; Okazaki, T. Sphingomyelin