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Tytuł:
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A DNA-encoded library for the identification of natural product binders that modulate poly (ADP-ribose) polymerase 1, a validated anti-cancer target.
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Autorzy:
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Li J; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, China; University of Chinese Academy of Sciences, 100049, Beijing, China.
Li Y; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, China; University of Chinese Academy of Sciences, 100049, Beijing, China.
Lu F; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
Liu L; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
Ji Q; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
Song K; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
Yin Q; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
Lerner RA; Department of Chemistry, Scripps Research Institute, La Jolla, CA, 92037, USA.
Yang G; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
Xu H; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China. Electronic address: .
Ma P; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China. Electronic address: .
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Źródło:
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Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Dec 03; Vol. 533 (2), pp. 241-248. Date of Electronic Publication: 2020 May 04.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
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MeSH Terms:
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DNA/*chemistry
Poly (ADP-Ribose) Polymerase-1/*metabolism
Poly(ADP-ribose) Polymerase Inhibitors/*chemistry
Poly(ADP-ribose) Polymerase Inhibitors/*pharmacology
Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Biological Products/chemical synthesis ; Biological Products/chemistry ; Biological Products/pharmacology ; Cell Line, Tumor ; DNA/chemical synthesis ; Drug Discovery ; Drug Evaluation, Preclinical ; Humans ; Luteolin/chemical synthesis ; Luteolin/chemistry ; Luteolin/pharmacology ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors ; Poly(ADP-ribose) Polymerase Inhibitors/chemical synthesis ; Protein Binding ; Small Molecule Libraries/chemical synthesis ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Surface Plasmon Resonance
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Contributed Indexing:
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Keywords: DNA-Encoded library; Drug discovery; Luteolin; Natural products; PARP1
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Substance Nomenclature:
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0 (Antineoplastic Agents)
0 (Biological Products)
0 (Poly(ADP-ribose) Polymerase Inhibitors)
0 (Small Molecule Libraries)
9007-49-2 (DNA)
EC 2.4.2.30 (PARP1 protein, human)
EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
KUX1ZNC9J2 (Luteolin)
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Entry Date(s):
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Date Created: 20200509 Date Completed: 20210316 Latest Revision: 20210316
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Update Code:
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20240105
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DOI:
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10.1016/j.bbrc.2020.04.022
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PMID:
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32381359
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Natural products have been an invaluable source of drug discovery, but their targets remain largely unknown. Natural products enriched DNA-encoded chemical libraries (nDELs) empower the researchers to rapidly and economically screen numerous natural products against various protein targets, and therefore promote the elucidation of the molecular mechanisms. In this work, we used poly (ADP-ribose) polymerase 1 (PARP1), as an example to explore the usage of nDEL for the functional natural products selection. We used late-stage modification approach to label three positive binders with unique DNA barcodes, whose dissociation constants range from sub-micromolar to micromolar. The selection criterion was set up according to the enrichment of these controls. Five natural products selected by this criterion directly bind to PARP1 in SPR, among which luteolin exhibits the highest inhibitory activity against PARP1. Moreover, luteolin selectively induces accumulation of DNA double-strand breaks and G2/M phase arrest in BRCA-deficient cells. All the findings from these investigations on luteolin support that PARP1 inhibition is one of the mechanisms for its anti-cancer activity.
(Copyright © 2020. Published by Elsevier Inc.)
