Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-09-10DOI: 10.1016/j.chembiol.2015.08.007
Lingling Duan, Ganesha Rai, Carlos Roggero, Qing-Jun Zhang, Qun Wei, Shi Hong Ma, Yunyun Zhou, John Santoyo, Elisabeth D Martinez, Guanghua Xiao, Ganesh V Raj, Ajit Jadhav, Anton Simeonov, David J Maloney, Josep Rizo, Jer-Tsong Hsieh, Zhi-Ping Liu
{"title":"KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by Suppressing the Expression of AR and BMYB-Regulated Genes.","authors":"Lingling Duan, Ganesha Rai, Carlos Roggero, Qing-Jun Zhang, Qun Wei, Shi Hong Ma, Yunyun Zhou, John Santoyo, Elisabeth D Martinez, Guanghua Xiao, Ganesh V Raj, Ajit Jadhav, Anton Simeonov, David J Maloney, Josep Rizo, Jer-Tsong Hsieh, Zhi-Ping Liu","doi":"10.1016/j.chembiol.2015.08.007","DOIUrl":"10.1016/j.chembiol.2015.08.007","url":null,"abstract":"<p><p>Histone lysine demethylase KDM4/JMJD2s are overexpressed in many human tumors including prostate cancer (PCa). KDM4s are co-activators of androgen receptor (AR) and are thus potential therapeutic targets. Yet to date few KDM4 inhibitors that have anti-prostate tumor activity in vivo have been developed. Here, we report the anti-tumor growth effect and molecular mechanisms of three novel KDM4 inhibitors (A1, I9, and B3). These inhibitors repressed the transcription of both AR and BMYB-regulated genes. Compound B3 is highly selective for a variety of cancer cell lines including PC3 cells that lack AR. B3 inhibited the in vivo growth of tumors derived from PC3 cells and ex vivo human PCa explants. We identified a novel mechanism by which KDM4B activates the transcription of Polo-like kinase 1 (PLK1). B3 blocked the binding of KDM4B to the PLK1 promoter. Our studies suggest a potential mechanism-based therapeutic strategy for PCa and tumors with elevated KDM4B/PLK1 expression.</p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1185-96"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578295/pdf/nihms719015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34066917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-07-23DOI: 10.1016/j.chembiol.2015.06.020
Claire N Bedbrook, Mihoko Kato, Sripriya Ravindra Kumar, Anupama Lakshmanan, Ravi D Nath, Fei Sun, Paul W Sternberg, Frances H Arnold, Viviana Gradinaru
{"title":"Genetically Encoded Spy Peptide Fusion System to Detect Plasma Membrane-Localized Proteins In Vivo.","authors":"Claire N Bedbrook, Mihoko Kato, Sripriya Ravindra Kumar, Anupama Lakshmanan, Ravi D Nath, Fei Sun, Paul W Sternberg, Frances H Arnold, Viviana Gradinaru","doi":"10.1016/j.chembiol.2015.06.020","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.06.020","url":null,"abstract":"<p><p>Membrane proteins are the main gatekeepers of cellular state, especially in neurons, serving either to maintain homeostasis or instruct response to synaptic input or other external signals. Visualization of membrane protein localization and trafficking in live cells facilitates understanding the molecular basis of cellular dynamics. We describe here a method for specifically labeling the plasma membrane-localized fraction of heterologous membrane protein expression using channelrhodopsins as a case study. We show that the genetically encoded, covalent binding SpyTag and SpyCatcher pair from the Streptococcus pyogenes fibronectin-binding protein FbaB can selectively label membrane-localized proteins in living cells in culture and in vivo in Caenorhabditis elegans. The SpyTag/SpyCatcher covalent labeling method is highly specific, modular, and stable in living cells. We have used the binding pair to develop a channelrhodopsin membrane localization assay that is amenable to high-throughput screening for opsin discovery and engineering. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1108-21"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.06.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33867885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-07-16DOI: 10.1016/j.chembiol.2015.06.017
Amber N Murray, Wentao Chen, Aristotelis Antonopoulos, Sarah R Hanson, R Luke Wiseman, Anne Dell, Stuart M Haslam, David L Powers, Evan T Powers, Jeffery W Kelly
{"title":"Enhanced Aromatic Sequons Increase Oligosaccharyltransferase Glycosylation Efficiency and Glycan Homogeneity.","authors":"Amber N Murray, Wentao Chen, Aristotelis Antonopoulos, Sarah R Hanson, R Luke Wiseman, Anne Dell, Stuart M Haslam, David L Powers, Evan T Powers, Jeffery W Kelly","doi":"10.1016/j.chembiol.2015.06.017","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.06.017","url":null,"abstract":"<p><p>N-Glycosylation plays an important role in protein folding and function. Previous studies demonstrate that a phenylalanine residue introduced at the n-2 position relative to an Asn-Xxx-Thr/Ser N-glycosylation sequon increases the glycan occupancy of the sequon in insect cells. Here, we show that any aromatic residue at n-2 increases glycan occupancy in human cells and that this effect is dependent upon oligosaccharyltransferase substrate preferences rather than differences in other cellular processing events such as degradation or trafficking. Moreover, aromatic residues at n-2 alter glycan processing in the Golgi, producing proteins with less complex N-glycan structures. These results demonstrate that manipulating the sequence space surrounding N-glycosylation sequons is useful both for controlling glycosylation efficiency, thus enhancing glycan occupancy, and for influencing the N-glycan structures produced. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1052-62"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.06.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33918760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-08-13DOI: 10.1016/j.chembiol.2015.07.013
Nicholas Chim, Rodrigo Torres, Yuqi Liu, Joe Capri, Gaëlle Batot, Julian P Whitelegge, Celia W Goulding
{"title":"The Structure and Interactions of Periplasmic Domains of Crucial MmpL Membrane Proteins from Mycobacterium tuberculosis.","authors":"Nicholas Chim, Rodrigo Torres, Yuqi Liu, Joe Capri, Gaëlle Batot, Julian P Whitelegge, Celia W Goulding","doi":"10.1016/j.chembiol.2015.07.013","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.013","url":null,"abstract":"<p><p>Mycobacterium tuberculosis mycobacterial membrane protein large (MmpL) proteins are important in substrate transport across the inner membrane. Here, we show that MmpL proteins are classified into two phylogenetic clusters, where MmpL cluster II contains three soluble domains (D1, D2, and D3) and has two full-length members, MmpL3 and MmpL11. Significantly, MmpL3 is currently the most druggable M. tuberculosis target. We have solved the 2.4-Å MmpL11-D2 crystal structure, revealing structural homology to periplasmic porter subdomains of RND (multidrug) transporters. The resulting predicted cluster II MmpL membrane topology has D1 and D2 residing, and possibly interacting, within the periplasm. Crosslinking and biolayer interferometry experiments confirm that cluster II D1 and D2 bind with weak affinities, and guided D1-D2 heterodimeric model assemblies. The predicted full-length MmpL3 and MmpL11 structural models reveal key substrate binding and transport residues, and may serve as templates to set the stage for in silico anti-tuberculosis drug development. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1098-107"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33924287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity.","authors":"Wei-jia Wang, Yuan Wang, Pei-pei Hou, Feng-wei Li, Bo Zhou, Hang-zi Chen, Xue-li Bian, Qi-xu Cai, Yong-zhen Xing, Jian-ping He, Hongkui Zhang, Pei-qiang Huang, Tianwei Lin, Qiao Wu","doi":"10.1016/j.chembiol.2015.06.023","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.06.023","url":null,"abstract":"<p><p>Apoptotic resistance is becoming a significant obstacle for cancer therapy as the majority of treatment takes the route of apoptotic induction. It is of great importance to develop an alternative strategy to induce cancer cell death. We previously reported that autophagic cell death mediated by nuclear receptor TR3 and driven by a chemical agonist, 1-(3,4,5-trihydroxyphenyl)nonan-1-one (THPN), is highly effective in the therapy of melanoma but not any other cancer types. Here, we discovered that the insensitivity of cancer cells to THPN originated from a high cellular Akt2 activity. Akt2 phosphorylation interferes with TR3 export to cytoplasm and targeting to mitochondria, which lead to the autophagic induction. Therefore, the TR3-mediated autophagy could be effectively induced in the otherwise insensitive cells by downregulating Akt2 activity. Highly effective antineoplastic compounds are developed through optimizing the structure of THPN. This study implicates a general strategy for cancer therapy by the induction of autophagic cell death. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1040-51"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.06.023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33888272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-08-13DOI: 10.1016/j.chembiol.2015.07.011
Yingjie Peng, Wenwen Zeng, Hui Ye, Kyung Ho Han, Venkatasubramanian Dharmarajan, Scott Novick, Ian A Wilson, Patrick R Griffin, Jeffrey M Friedman, Richard A Lerner
{"title":"A General Method for Insertion of Functional Proteins within Proteins via Combinatorial Selection of Permissive Junctions.","authors":"Yingjie Peng, Wenwen Zeng, Hui Ye, Kyung Ho Han, Venkatasubramanian Dharmarajan, Scott Novick, Ian A Wilson, Patrick R Griffin, Jeffrey M Friedman, Richard A Lerner","doi":"10.1016/j.chembiol.2015.07.011","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.011","url":null,"abstract":"<p><p>A major goal of modern protein chemistry is to create new proteins with different functions. One approach is to amalgamate secondary and tertiary structures from different proteins. This is difficult for several reasons, not the least of which is the fact that the junctions between secondary and tertiary structures are not degenerate and usually affect the function and folding of the entire complex. Here, we offer a solution to this problem by coupling a large combinatorial library of about 10(7) different N- and C-terminal junctions to a powerful system that selects for function. Using this approach, the entire Leptin and follicle-stimulating hormone (FSH) were inserted into an antibody. Complexes with full retention of function in vivo and in vitro, although rare, were found easily by using an autocrine selection system to search for hormonal activity. Such large diversity systems, when coupled to robust selection systems, should enable construction of novel therapeutic proteins. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1134-43"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33924288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-08-06DOI: 10.1016/j.chembiol.2015.07.008
Muskan Kukreja, Sergey A Shiryaev, Piotr Cieplak, Norihito Muranaka, David A Routenberg, Andrei V Chernov, Sonu Kumar, Albert G Remacle, Jeffrey W Smith, Igor A Kozlov, Alex Y Strongin
{"title":"High-Throughput Multiplexed Peptide-Centric Profiling Illustrates Both Substrate Cleavage Redundancy and Specificity in the MMP Family.","authors":"Muskan Kukreja, Sergey A Shiryaev, Piotr Cieplak, Norihito Muranaka, David A Routenberg, Andrei V Chernov, Sonu Kumar, Albert G Remacle, Jeffrey W Smith, Igor A Kozlov, Alex Y Strongin","doi":"10.1016/j.chembiol.2015.07.008","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.008","url":null,"abstract":"<p><p>Matrix metalloproteinases (MMPs) play incompletely understood roles in health and disease. Knowing the MMP cleavage preferences is essential for a better understanding of the MMP functions and design of selective inhibitors. To elucidate the cleavage preferences of MMPs, we employed a high-throughput multiplexed peptide-centric profiling technology involving the cleavage of 18,583 peptides by 18 proteinases from the main sub-groups of the MMP family. Our results enabled comparison of the MMP substrates on a global scale, leading to the most efficient and selective substrates. The data validated the accuracy of our cleavage prediction software. This software allows us and others to locate, with nearly 100% accuracy, the MMP cleavage sites in the peptide sequences. In addition to increasing our understanding of both the selectivity and the redundancy of the MMP family, our study generated a roadmap for the subsequent MMP structural-functional studies and efficient substrate and inhibitor design. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1122-33"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33905810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-08-06DOI: 10.1016/j.chembiol.2015.07.007
Laura M Castellano, Stephen M Bart, Veronica M Holmes, Drew Weissman, James Shorter
{"title":"Repurposing Hsp104 to Antagonize Seminal Amyloid and Counter HIV Infection.","authors":"Laura M Castellano, Stephen M Bart, Veronica M Holmes, Drew Weissman, James Shorter","doi":"10.1016/j.chembiol.2015.07.007","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.007","url":null,"abstract":"<p><p>Naturally occurring proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and SEM2) form amyloid fibrils in seminal fluid, which capture HIV virions and promote infection. For example, PAP248-286 fibrils, termed SEVI (semen-derived enhancer of viral infection), can potentiate HIV infection by several orders of magnitude. Here, we design three disruptive technologies to rapidly antagonize seminal amyloid by repurposing Hsp104, an amyloid-remodeling nanomachine from yeast. First, Hsp104 and an enhanced engineered variant, Hsp104(A503V), directly remodel SEVI and PAP85-120 fibrils into non-amyloid forms. Second, we elucidate catalytically inactive Hsp104 scaffolds that do not remodel amyloid structure, but cluster SEVI, PAP85-120, and SEM1(45-107) fibrils into larger assemblies. Third, we modify Hsp104 to interact with the chambered protease ClpP, which enables coupled remodeling and degradation to irreversibly clear SEVI and PAP85-120 fibrils. Each strategy diminished the ability of seminal amyloid to promote HIV infection, and could have therapeutic utility. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1074-86"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33905813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-08-13DOI: 10.1016/j.chembiol.2015.07.012
Sónia Troeira Henriques, Yen-Hua Huang, Stephanie Chaousis, Marc-Antoine Sani, Aaron G Poth, Frances Separovic, David J Craik
{"title":"The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells.","authors":"Sónia Troeira Henriques, Yen-Hua Huang, Stephanie Chaousis, Marc-Antoine Sani, Aaron G Poth, Frances Separovic, David J Craik","doi":"10.1016/j.chembiol.2015.07.012","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.012","url":null,"abstract":"<p><p>Cyclotides combine the stability of disulfide-rich peptides with the intracellular accessibility of cell-penetrating peptides, giving them outstanding potential as drug scaffolds with an ability to inhibit intracellular protein-protein interactions. To realize and optimize the application of cyclotides as a drug framework and delivery system, we studied the ability of the prototypic cyclotide, kalata B1, to enter mammalian cells. We show that kalata B1 can enter cells via both endocytosis and direct membrane translocation. Both pathways are initiated by targeting phosphatidylethanolamine phospholipids at the cell surface and inducing membrane curvature. This unusual approach to initiate internalization might be harnessed to deliver drugs into cells and, in particular, cancer cells, which present a higher proportion of surface-exposed phosphatidylethanolamine phospholipids. Our findings highlight the potential of these peptides as drug leads for the modulation of traditionally \"undruggable\" targets, such as intracellular protein-protein interactions. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1087-97"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33924286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-08-20Epub Date: 2015-07-23DOI: 10.1016/j.chembiol.2015.06.021
Agnieszka Szwajda, Prson Gautam, Leena Karhinen, Sawan Kumar Jha, Jani Saarela, Sushil Shakyawar, Laura Turunen, Bhagwan Yadav, Jing Tang, Krister Wennerberg, Tero Aittokallio
{"title":"Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles.","authors":"Agnieszka Szwajda, Prson Gautam, Leena Karhinen, Sawan Kumar Jha, Jani Saarela, Sushil Shakyawar, Laura Turunen, Bhagwan Yadav, Jing Tang, Krister Wennerberg, Tero Aittokallio","doi":"10.1016/j.chembiol.2015.06.021","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.06.021","url":null,"abstract":"<p><p>Chemical perturbation screens offer the possibility to identify actionable sets of cancer-specific vulnerabilities. However, most inhibitors of kinases or other cancer targets result in polypharmacological effects, which complicate the identification of target dependencies directly from the drug-response phenotypes. In this study, we developed a chemical systems biology approach that integrates comprehensive drug sensitivity and selectivity profiling to provide functional insights into both single and multi-target oncogenic signal addictions. When applied to 21 breast cancer cell lines, perturbed with 40 kinase inhibitors, the subtype-specific addiction patterns clustered in agreement with patient-derived subtypes, while showing considerable variability between the heterogeneous breast cancers. Experimental validation of the top predictions revealed a number of co-dependencies between kinase targets that led to unexpected synergistic combinations between their inhibitors, such as dasatinib and axitinib in the triple-negative basal-like HCC1937 cell line. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 8","pages":"1144-55"},"PeriodicalIF":0.0,"publicationDate":"2015-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.06.021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33867881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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