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Article: Comprehensive Structure-Activity Relationship Studies of Cepafungin Enabled by Biocatalytic C-H Oxidations.

Amatuni, Alexander / Shuster, Anton / Abegg, Daniel / Adibekian, Alexander / Renata, Hans

ACS central science

2023 Volume 9, Issue 2, Page(s) 239–251

Abstract: The cepafungins are a class of highly potent and selective eukaryotic proteasome inhibitor natural products with potential to treat refractory multiple myeloma and other cancers. The structure-activity relationship of the cepafungins is not fully ... ...

Abstract	The cepafungins are a class of highly potent and selective eukaryotic proteasome inhibitor natural products with potential to treat refractory multiple myeloma and other cancers. The structure-activity relationship of the cepafungins is not fully understood. This Article chronicles the development of a chemoenzymatic approach to cepafungin I. A failed initial route involving derivatization of pipecolic acid prompted us to examine the biosynthetic pathway for the production of 4-hydroxylysine, which culminated in the development of a 9-step synthesis of cepafungin I. An alkyne-tagged analogue enabled chemoproteomic studies of cepafungin and comparison of its effects on global protein expression in human multiple myeloma cells to the clinical drug bortezomib. A preliminary series of analogues elucidated critical determinants of potency in proteasome inhibition. Herein we report the chemoenzymatic syntheses of 13 additional analogues of cepafungin I guided by a proteasome-bound crystal structure, 5 of which are more potent than the natural product. The lead analogue was found to have 7-fold greater proteasome β5 subunit inhibitory activity and has been evaluated against several multiple myeloma and mantle cell lymphoma cell lines in comparison to the clinical drug bortezomib.
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Journal Article
ISSN	2374-7943
ISSN	2374-7943
DOI	10.1021/acscentsci.2c01219
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Concise Chemoenzymatic Total Synthesis and Identification of Cellular Targets of Cepafungin I.

Amatuni, Alexander / Shuster, Anton / Adibekian, Alexander / Renata, Hans

Cell chemical biology

2020 Volume 27, Issue 10, Page(s) 1318–1326.e18

Abstract: The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin ...

Abstract	The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to prepare a key hydroxylated amino acid building block in a scalable fashion. The strategy developed herein enabled access to a chemoproteomic probe, which in turn revealed the exceptional selectivity and potency of cepafungin I toward the β2 and β5 subunits of the proteasome. Further structure-activity relationship studies suggest the key role of the hydroxyl group in the macrocycle and the identity of the lipid tail in modulating the potency of this natural product family. This study lays the groundwork for further medicinal chemistry exploration to fully realize the anticancer potential of cepafungin I.
MeSH term(s)	Cells, Cultured ; Humans ; Molecular Structure ; Peptides, Cyclic/chemical synthesis ; Peptides, Cyclic/chemistry ; Peptides, Cyclic/pharmacology ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Inhibitors/chemical synthesis ; Proteasome Inhibitors/chemistry ; Proteasome Inhibitors/pharmacology ; Stereoisomerism ; Structure-Activity Relationship
Chemical Substances	Peptides, Cyclic ; Proteasome Inhibitors ; cepafungin I (130743-08-7) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2020-08-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2020.07.012
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Article ; Online: Optical Control of Proteasomal Protein Degradation with a Photoswitchable Lipopeptide.

Morstein, Johannes / Amatuni, Alexander / Shuster, Anton / Kuttenlochner, Wolfgang / Ko, Tongil / Abegg, Daniel / Groll, Michael / Adibekian, Alexander / Renata, Hans / Trauner, Dirk H

Angewandte Chemie (International ed. in English)

2024 Volume 63, Issue 8, Page(s) e202314791

Abstract: Photolipids have emerged as attractive tools for the optical control of lipid functions. They often contain an azobenzene photoswitch that imparts a cis double-bond upon irradiation. Herein, we present the application of photoswitching to a lipidated ... ...

Abstract	Photolipids have emerged as attractive tools for the optical control of lipid functions. They often contain an azobenzene photoswitch that imparts a cis double-bond upon irradiation. Herein, we present the application of photoswitching to a lipidated natural product, the potent proteasome inhibitor cepafungin I. Several azobenzene-containing lipids were attached to the cyclopeptide core, yielding photoswitchable derivatives. Most notably, PhotoCep4 exhibited a 10-fold higher cellular potency in its light-induced cis-form, matching the potency of natural cepafungin I. The length of the photolipid tail and distal positioning of the azobenzene photoswitch with respect to the macrocycle is critical for this activity. In a proteome-wide experiment, light-triggered PhotoCep4 modulation showed high overlap with constitutively active cepafungin I. The mode of action was studied using crystallography and revealed an identical binding of the cyclopeptide in comparison to cepafungin I, suggesting that differences in their cellular activity originate from switching the tail structure. The photopharmacological approach described herein could be applicable to many other natural products as lipid conjugation is common and often necessary for potent activity. Such lipids are often introduced late in synthetic routes, enabling facile chemical modifications.
MeSH term(s)	Lipopeptides/pharmacology ; Proteolysis ; Azo Compounds/chemistry ; Peptides, Cyclic/pharmacology
Chemical Substances	azobenzene (F0U1H6UG5C) ; Lipopeptides ; Azo Compounds ; Peptides, Cyclic
Language	English
Publishing date	2024-01-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202314791
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Article ; Online: Clinical Antiviral Drug Arbidol Inhibits Infection by SARS-CoV-2 and Variants through Direct Binding to the Spike Protein.

Shuster, Anton / Pechalrieu, Dany / Jackson, Cody B / Abegg, Daniel / Choe, Hyeryun / Adibekian, Alexander

ACS chemical biology

2021 Volume 16, Issue 12, Page(s) 2845–2851

Abstract: Arbidol (ARB) is a broad-spectrum antiviral drug approved in Russia and China for the treatment of influenza. ARB was tested in patients as a drug candidate for the treatment at the early onset of COVID-19 caused by the novel severe acute respiratory ... ...

Abstract	Arbidol (ARB) is a broad-spectrum antiviral drug approved in Russia and China for the treatment of influenza. ARB was tested in patients as a drug candidate for the treatment at the early onset of COVID-19 caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite promising clinical results and multiple ongoing trials, preclinical data are lacking and the molecular mechanism of action of ARB against SARS-CoV-2 remains unknown. Here, we demonstrate that ARB binds to the spike viral fusion glycoprotein of the SARS-CoV-2 Wuhan strain as well as its more virulent variants from the United Kingdom (strain B.1.1.7) and South Africa (strain B.1.351). We pinpoint the ARB binding site on the S protein to the S2 membrane fusion domain and use an infection assay with Moloney murine leukemia virus (MLV) pseudoviruses (PVs) pseudotyped with the S proteins of the Wuhan strain and the new variants to show that this interaction is sufficient for the viral cell entry inhibition by ARB. Finally, our experiments reveal that the ARB interaction leads to a significant destabilization and eventual lysosomal degradation of the S protein in cells. Collectively, our results identify ARB as the first clinically approved small molecule drug binder of the SARS-CoV-2 S protein and place ARB among the more promising drug candidates for COVID-19.
MeSH term(s)	A549 Cells ; Animals ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacology ; Binding Sites ; Chlorocebus aethiops ; HEK293 Cells ; Humans ; Indoles/metabolism ; Indoles/pharmacology ; Lysosomes/metabolism ; Mutation ; Protein Domains ; Proteolysis/drug effects ; SARS-CoV-2/drug effects ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Vero Cells ; Virus Internalization/drug effects
Chemical Substances	Antiviral Agents ; Indoles ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; umifenovir (93M09WW4RU)
Language	English
Publishing date	2021-11-18
Publishing country	United States
Document type	Journal Article
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.1c00756
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Article ; Online: Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway.

Abegg, Daniel / Tomanik, Martin / Qiu, Nan / Pechalrieu, Dany / Shuster, Anton / Commare, Bruno / Togni, Antonio / Herzon, Seth B / Adibekian, Alexander

Journal of the American Chemical Society

2021 Volume 143, Issue 48, Page(s) 20332–20342

Abstract: Chemoproteomic profiling of cysteines has emerged as a powerful method for screening the proteome-wide targets of cysteine-reactive fragments, drugs, and natural products. Herein, we report the development and an in-depth evaluation of a tetrafluoroalkyl ...

Abstract	Chemoproteomic profiling of cysteines has emerged as a powerful method for screening the proteome-wide targets of cysteine-reactive fragments, drugs, and natural products. Herein, we report the development and an in-depth evaluation of a tetrafluoroalkyl benziodoxole (TFBX) as a cysteine-selective chemoproteomic probe. We show that this probe features numerous key improvements compared to the traditionally used cysteine-reactive probes, including a superior target occupancy, faster labeling kinetics, and broader proteomic coverage, thus enabling profiling of cysteines directly in live cells. In addition, the fluorine "signature" of probe
MeSH term(s)	Alkylation ; Cysteine/chemistry ; DNA End-Joining Repair/drug effects ; Diterpenes/pharmacology ; Enzyme Inhibitors/pharmacology ; HEK293 Cells ; HeLa Cells ; Heterocyclic Compounds, 2-Ring/chemistry ; Humans ; Hydrocarbons, Fluorinated/chemistry ; Ku Autoantigen/antagonists & inhibitors ; Ku Autoantigen/chemistry ; Molecular Probes/chemistry ; Proteomics/methods
Chemical Substances	Diterpenes ; Enzyme Inhibitors ; Heterocyclic Compounds, 2-Ring ; Hydrocarbons, Fluorinated ; Molecular Probes ; XRCC5 protein, human (EC 3.6.4.12) ; Ku Autoantigen (EC 4.2.99.-) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2021-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.1c09724
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Article ; Online: Targeted Degradation of the Oncogenic MicroRNA 17-92 Cluster by Structure-Targeting Ligands.

Liu, Xiaohui / Haniff, Hafeez S / Childs-Disney, Jessica L / Shuster, Anton / Aikawa, Haruo / Adibekian, Alexander / Disney, Matthew D

Journal of the American Chemical Society

2020 Volume 142, Issue 15, Page(s) 6970–6982

Abstract: Many RNAs are processed into biologically active transcripts, the aberrant expression of which can contribute to disease phenotypes. For example, the primary microRNA-17-92 (pri-miR-17-92) cluster contains six microRNAs (miRNAs) that collectively act in ... ...

Abstract	Many RNAs are processed into biologically active transcripts, the aberrant expression of which can contribute to disease phenotypes. For example, the primary microRNA-17-92 (pri-miR-17-92) cluster contains six microRNAs (miRNAs) that collectively act in several disease settings. Herein, we used sequence-based design of structure-specific ligands to target a common structure in the Dicer processing sites of three miRNAs in the cluster, miR-17, miR-18a, and miR-20a, thereby inhibiting their biogenesis. The compound was optimized to afford a dimeric molecule that binds the Dicer processing site and an adjacent bulge, affording a 100-fold increase in potency. The dimer's mode of action was then extended from simple binding to direct cleavage by conjugation to bleomycin A5 in a manner that imparts RNA-selective cleavage or to indirect cleavage by recruiting an endogenous nuclease, or a ribonuclease targeting chimera (RIBOTAC). Interestingly, the dimer-bleomycin conjugate cleaves the entire pri-miR-17-92 cluster and hence functionally inhibits all six miRNAs emanating from it. The compound selectively reduced levels of the cluster in three disease models: polycystic kidney disease, prostate cancer, and breast cancer, rescuing disease-associated phenotypes in the latter two. Further, the bleomycin conjugate exerted selective effects on the miRNome and proteome in prostate cancer cells. In contrast, the RIBOTAC only depleted levels of pre- and mature miR-17, -18a, and 20a, with no effect on the primary transcript, in accordance with the cocellular localization of RNase L, the pre-miRNA targets, and the compound. These studies demonstrate a strategy to tune RNA structure-targeting compounds to the cellular localization of the target.
MeSH term(s)	Carcinogenesis/metabolism ; Humans ; Ligands ; MicroRNAs/metabolism ; Molecular Structure
Chemical Substances	Ligands ; MIRN17 microRNA, human ; MicroRNAs
Language	English
Publishing date	2020-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.9b13159
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Article: Targeted Degradation of the Oncogenic MicroRNA 17-92 Cluster by Structure-Targeting Ligands

Liu, Xiaohui / Haniff, Hafeez S / Childs-Disney, Jessica L / Shuster, Anton / Aikawa, Haruo / Adibekian, Alexander / Disney, Matthew D

Journal of the American Chemical Society. 2020 Apr. 01, v. 142, no. 15

2020

Abstract	Many RNAs are processed into biologically active transcripts, the aberrant expression of which can contribute to disease phenotypes. For example, the primary microRNA-17-92 (pri-miR-17-92) cluster contains six microRNAs (miRNAs) that collectively act in several disease settings. Herein, we used sequence-based design of structure-specific ligands to target a common structure in the Dicer processing sites of three miRNAs in the cluster, miR-17, miR-18a, and miR-20a, thereby inhibiting their biogenesis. The compound was optimized to afford a dimeric molecule that binds the Dicer processing site and an adjacent bulge, affording a 100-fold increase in potency. The dimer’s mode of action was then extended from simple binding to direct cleavage by conjugation to bleomycin A5 in a manner that imparts RNA-selective cleavage or to indirect cleavage by recruiting an endogenous nuclease, or a ribonuclease targeting chimera (RIBOTAC). Interestingly, the dimer-bleomycin conjugate cleaves the entire pri-miR-17-92 cluster and hence functionally inhibits all six miRNAs emanating from it. The compound selectively reduced levels of the cluster in three disease models: polycystic kidney disease, prostate cancer, and breast cancer, rescuing disease-associated phenotypes in the latter two. Further, the bleomycin conjugate exerted selective effects on the miRNome and proteome in prostate cancer cells. In contrast, the RIBOTAC only depleted levels of pre- and mature miR-17, -18a, and 20a, with no effect on the primary transcript, in accordance with the cocellular localization of RNase L, the pre-miRNA targets, and the compound. These studies demonstrate a strategy to tune RNA structure-targeting compounds to the cellular localization of the target.
Keywords	biogenesis ; breast neoplasms ; disease models ; ligands ; mechanism of action ; messenger RNA ; microRNA ; neoplasm cells ; phenotype ; polycystic kidney diseases ; prostatic neoplasms ; proteome ; ribonucleases
Language	English
Dates of publication	2020-0401
Size	p. 6970-6982.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.9b13159
Database	NAL-Catalogue (AGRICOLA)

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Article: Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway

Abegg, Daniel / Tomanik, Martin / Qiu, Nan / Pechalrieu, Dany / Shuster, Anton / Commare, Bruno / Togni, Antonio / Herzon, Seth B. / Adibekian, Alexander

Journal of the American Chemical Society. 2021 Nov. 24, v. 143, no. 48

2021

Abstract	Chemoproteomic profiling of cysteines has emerged as a powerful method for screening the proteome-wide targets of cysteine-reactive fragments, drugs, and natural products. Herein, we report the development and an in-depth evaluation of a tetrafluoroalkyl benziodoxole (TFBX) as a cysteine-selective chemoproteomic probe. We show that this probe features numerous key improvements compared to the traditionally used cysteine-reactive probes, including a superior target occupancy, faster labeling kinetics, and broader proteomic coverage, thus enabling profiling of cysteines directly in live cells. In addition, the fluorine “signature” of probe 7 constitutes an additional advantage resulting in a more confident adduct–amino acid site assignment in mass-spectrometry-based identification workflows. We demonstrate the utility of our new probe for proteome-wide target profiling by identifying the cellular targets of (−)-myrocin G, an antiproliferative fungal natural product with a to-date unknown mechanism of action. We show that this natural product and a simplified analogue target the X-ray repair cross-complementing protein 5 (XRCC5), an ATP-dependent DNA helicase that primes DNA repair machinery for nonhomologous end joining (NHEJ) upon DNA double-strand breaks, making them the first reported inhibitors of this biomedically highly important protein. We further demonstrate that myrocins disrupt the interaction of XRCC5 with DNA leading to sensitization of cancer cells to the chemotherapeutic agent etoposide as well as UV-light-induced DNA damage. Altogether, our next-generation cysteine-reactive probe enables broader and deeper profiling of the cysteinome, rendering it a highly attractive tool for elucidation of targets of electrophilic small molecules.
Keywords	DNA ; DNA damage ; DNA helicases ; DNA repair ; Lewis acids ; X-radiation ; cysteine ; drug therapy ; etoposide ; fluorine ; fungi ; mechanism of action ; proteomics
Language	English
Dates of publication	2021-1124
Size	p. 20332-20342.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.1c09724
Database	NAL-Catalogue (AGRICOLA)

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Article: Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study.

Anton, Stephen D / Shuster, Jonathan / Leeuwenburgh, Christiaan

Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine

2011 Volume 9, Issue 11, Page(s) 1190–1198

Abstract: Background: Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake ... ...

Abstract	Background: Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is hydroxycitric acid (HCA) derived from Garcinia cambogia Desr. Methods and design: The objective of this article is to describe the protocol of a clinical trial designed to directly test the effects of Garcinia cambogia-derived HCA on food intake, satiety, weight loss and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight or obese individuals (with a body mass index range of 25.0 to 39.9 kg/m(2)) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day. This study can be completed with far fewer subjects than a parallel design. Discussion: Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA is selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial. Trial registration: ClinicalTrials.gov (Identifier: NCT01238887).
MeSH term(s)	Aged ; Cross-Over Studies ; Double-Blind Method ; Drugs, Chinese Herbal/pharmacology ; Eating/drug effects ; Humans ; Middle Aged ; Overweight ; Oxidative Stress/drug effects ; Randomized Controlled Trials as Topic ; Research Design ; Satiation/drug effects ; Weight Loss/drug effects
Chemical Substances	Drugs, Chinese Herbal
Language	English
Publishing date	2011-11-17
Publishing country	China
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2229154-4
ISSN	1672-1977
ISSN	1672-1977
DOI	10.3736/jcim20111106
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Article ; Online: Combined Omics Approach Identifies Gambogic Acid and Related Xanthones as Covalent Inhibitors of the Serine Palmitoyltransferase Complex.

Hoch, Dominic G / Abegg, Daniel / Hannich, J Thomas / Pechalrieu, Dany / Shuster, Anton / Dwyer, Brendan G / Wang, Chao / Zhang, Xiaojin / You, Qidong / Riezman, Howard / Adibekian, Alexander

Cell chemical biology

2020 Volume 27, Issue 5, Page(s) 586–597.e12

Abstract: In this study, we identify the natural product gambogic acid as well as structurally related synthetic xanthones as first-in-class covalent inhibitors of the de novo sphingolipid biosynthesis. We apply chemoproteomics to determine that gambogic acid ... ...

Abstract	In this study, we identify the natural product gambogic acid as well as structurally related synthetic xanthones as first-in-class covalent inhibitors of the de novo sphingolipid biosynthesis. We apply chemoproteomics to determine that gambogic acid binds to the regulatory small subunit B of the serine palmitoyltransferase complex (SPTSSB). We then test structurally related synthetic xanthones to identify 18 as an equally potent but more selective binder of SPTSSB and show that 18 reduces sphingolipid levels in situ and in vivo. Finally, using various biological methods, we demonstrate that 18 induces cellular responses characteristic for diminished sphingosine-1-phosphate (S1P) signaling. This study demonstrates that SPTSSB may become a viable therapeutic target in various diseases with pathological S1P signaling. Furthermore, we believe that our compound will become a valuable tool for studying the sphingolipid metabolism and serve as a blueprint for the development of a new generation of sphingolipid biosynthesis inhibitors.
MeSH term(s)	Animals ; Drug Discovery ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; HEK293 Cells ; Humans ; Lysophospholipids/metabolism ; MCF-7 Cells ; Mice ; Mice, Inbred ICR ; Proteomics ; Serine C-Palmitoyltransferase/antagonists & inhibitors ; Serine C-Palmitoyltransferase/metabolism ; Sphingolipids/metabolism ; Sphingosine/analogs & derivatives ; Sphingosine/metabolism ; Xanthones/chemistry ; Xanthones/pharmacology
Chemical Substances	Enzyme Inhibitors ; Lysophospholipids ; Sphingolipids ; Xanthones ; sphingosine 1-phosphate (26993-30-6) ; gambogic acid (8N585K83U2) ; Serine C-Palmitoyltransferase (EC 2.3.1.50) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2020-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2020.03.008
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