ACS Combinatorial Science最新文献

{"title":"Confronting Racism in Chemistry Journals","authors":"Cynthia J. Burrows, Jiaxing Huang, Shu Wang, Hyun Jae Kim, Gerald J. Meyer, Kirk Schanze, T. Randall Lee, Jodie L. Lutkenhaus, David Kaplan, Christopher Jones, Carolyn Bertozzi, Laura Kiessling, Mary Beth Mulcahy, Craig W. Lindsley, M. G. Finn, Joel D. Blum, Prashant Kamat, Wonyong Choi, Shane Snyder, Courtney C. Aldrich, Stuart Rowan, Bin Liu, Dennis Liotta, Paul S. Weiss, Deqing Zhang, Krishna N. Ganesh, Harry A. Atwater, J. Justin Gooding, David T. Allen, Christopher A. Voigt, Jonathan Sweedler, Alanna Schepartz, Vincent Rotello, Sébastien Lecommandoux, Shana J. Sturla, Sharon Hammes-Schiffer, Jillian Buriak, Jonathan W. Steed, Hongwei Wu, Julie Zimmerman, Bryan Brooks, Phillip Savage, William Tolman, Thomas F. Hofmann, Joan F. Brennecke, Thomas A. Holme, Kenneth M. Merz Jr., Gustavo Scuseria, William Jorgensen, Gunda I. Georg, Shaomeng Wang, Philip Proteau, John R. Yates III, Peter Stang, Gilbert C. Walker, Marc Hillmyer, Lynne S. Taylor, Teri W. Odom, Erick Carreira, Kai Rossen, Paul Chirik, Scott J. Miller, Joan-Emma Shea, Anne McCoy, Martin Zanni, Gregory Hartland, Gregory Scholes, Joseph A. Loo, James Milne, Sarah B. Tegen, Daniel T. Kulp, Julia Laskin","doi":"10.1021/acscombsci.0c00121","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00121","url":null,"abstract":"W confront the terrible reality that systemic racism and discrimination impacts the daily personal and professional lives of many members of the scientific community and broader society. In the U.S., the brutal killing of George Floyd while in police custody is one of the most recent examples of the centuries of systemic violence suffered by Black Americans. This moment and its aftermath lay bare the legacies of racism and its exclusionary practices. Let us be clear: we, the Editors, Staff, and Governance Members of ACS Publications condemn the tragic deaths of Black people and stand in solidarity with Black members of the science and engineering community. Moreover, ACS condemns racism, discrimination, and harassment in all forms. We will not tolerate practices and viewpoints that exclude or demean any member of our community. Despite these good intentions, we recognize that our community has not done enough to provide an environment for Black chemists to thrive. Rep. Eddie Bernice Johnson, Chairwoman of the U.S. House Committee on Science, Space, and Technology said, “So far, we have gotten by with a STEM workforce that does not come close to representing the diversity of our nation. However, if we continue to leave behind so much of our nation’s brainpower, we cannot succeed.” Indeed, the U.S. National Science Foundation notes that Blacks and other under-represented minority groups continue to be under-represented in science and engineering education and employment. What is abundantly clear in this moment is that this lack of representation is a symptom of systemic racism across all levels of education and professional life. We know that supportive words are not enough. We must develop and implement a concrete plan for changing our trajectory. Publications and citations are academic currency, and while we like to think publishing a manuscript is “just about the science”, we know that is not true for everyone. We have seen the biases (largely through the lens of gender and in Western countries because of the limitations in bibliometric analyses) and applaud our colleagues at the RSC for their massive study that explored these gender barriers in the publishing pipeline and their recent Inclusion and Diversity Framework. At the present time, unfortunately, less is known about the effects of race and ethnicity on publishing success. A study published in PeerJ, however, found that unprofessional reviewer comments had a disproportionate effect on authors from underrepresented groups. As the world’s leading society publisher, we have a responsibility to aggressively combat bias in all aspects of the publishing process, including systemic under-representation of Blacks in this endeavor (no ACS journal is currently led by a Black Editor-in-Chief). Within ACS Publications, we actively track gender and geographic diversity of editors, advisors, authors, and reviewers, and we anecdotally report on race of editors. Diversity encompasses many more dimension","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"807485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Throughput and Autonomous Grazing Incidence X-ray Diffraction Mapping of Organic Combinatorial Thin-Film Library Driven by Machine Learning","authors":"Shingo Maruyama*,&nbsp;Kana Ouchi,&nbsp;Tomoyuki Koganezawa,&nbsp;Yuji Matsumoto*","doi":"10.1021/acscombsci.0c00037","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00037","url":null,"abstract":"<p >High-throughput X-ray diffraction (XRD) is one of the most indispensable techniques to accelerate materials research. However, the conventional XRD analysis with a large beam spot size may not best appropriate in a case for characterizing organic materials thin film libraries, in which various films prepared under different process conditions are integrated on a single substrate. Here, we demonstrate that high-resolution grazing incident XRD mapping analysis is useful for this purpose: A 2-dimensional organic combinatorial thin film library with the composition and growth temperature varied along the two orthogonal axes was successfully analyzed by using synchrotron microbeam X-ray. Moreover, we show that the time-consuming mapping process is accelerated with the aid of a machine learning technique termed as Bayesian optimization based on Gaussian process regression.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"801850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Denoising DNA Encoded Library Screens with Sparse Learning","authors":"Péter Kómár*,&nbsp;Marko Kalinić*","doi":"10.1021/acscombsci.0c00007","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00007","url":null,"abstract":"<p >DNA-encoded libraries (DELs) are large, pooled collections of compounds in which every library member is attached to a stretch of DNA encoding its complete synthetic history. DEL-based hit discovery involves affinity selection of the library against a protein of interest, whereby compounds retained by the target are subsequently identified by next-generation sequencing of the corresponding DNA tags. When analyzing the resulting data, one typically assumes that sequencing output (i.e., read counts) is proportional to the binding affinity of a given compound, thus enabling hit prioritization and elucidation of any underlying structure–activity relationships (SAR). This assumption, though, tends to be severely confounded by a number of factors, including variable reaction yields, presence of incomplete products masquerading as their intended counterparts, and sequencing noise. In practice, these confounders are often ignored, potentially contributing to low hit validation rates, and universally leading to loss of valuable information. To address this issue, we have developed a method for comprehensively denoising DEL selection outputs. Our method, dubbed “deldenoiser”, is based on sparse learning and leverages inputs that are commonly available within a DEL generation and screening workflow. Using simulated and publicly available DEL affinity selection data, we show that “deldenoiser” is not only able to recover and rank true binders much more robustly than read count-based approaches but also that it yields scores, which accurately capture the underlying SAR. The proposed method can, thus, be of significant utility in hit prioritization following DEL screens.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"736966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of High-Throughput Methyltransferase Assays for the Discovery of Small Molecule Inhibitors","authors":"Guangping Dong,&nbsp;Adam Yasgar,&nbsp;Darrell L. Peterson,&nbsp;Alexey Zakharov,&nbsp;Daniel Talley,&nbsp;Ken Chih-Chien Cheng,&nbsp;Ajit Jadhav,&nbsp;Anton Simeonov,&nbsp;Rong Huang*","doi":"10.1021/acscombsci.0c00077","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00077","url":null,"abstract":"Methyltransferases (MTases) play diverse roles in cellular processes. Aberrant methylation levels have been implicated in many diseases, indicating the need for the identification and development of small molecule inhibitors for each MTase. Specific inhibitors can serve as probes to investigate the function and validate therapeutic potential for the respective MTase. High-throughput screening (HTS) is a powerful method to identify initial hits for further optimization. Here, we report the development of a fluorescence-based MTase assay and compare this format with the recently developed MTase-Glo™ luminescence assay for the application in HTS. Using protein N-terminal methyltransferase 1 (NTMT1) as a model system, we miniaturized to 1,536-well quantitative HTS format. Through a pilot screen of 1,428 pharmacologically active compounds and subsequent validation, we discovered that MTase-Glo™ produced lower false positive rates than the fluorescence-based MTase assay. Nevertheless, both assays displayed robust performance along with low reagent requirements and can potentially be employed as general HTS formats for the discovery of inhibitors for any MTase.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"284005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A High-Throughput Structural and Electrochemical Study of Metallic Glass Formation in Ni–Ti–Al","authors":"Howie Joress*,&nbsp;Brian L. DeCost,&nbsp;Suchismita Sarker,&nbsp;Trevor M. Braun,&nbsp;Sidra Jilani,&nbsp;Ryan Smith,&nbsp;Logan Ward,&nbsp;Kevin J. Laws,&nbsp;Apurva Mehta,&nbsp;Jason R. Hattrick-Simpers","doi":"10.1021/acscombsci.9b00215","DOIUrl":"https://doi.org/10.1021/acscombsci.9b00215","url":null,"abstract":"<p >On the basis of a set of machine learning predictions of glass formation in the Ni–Ti–Al system, we have undertaken a high-throughput experimental study of that system. We utilized rapid synthesis followed by high-throughput structural and electrochemical characterization. Using this dual-modality approach, we are able to better classify the amorphous portion of the library, which we found to be the portion with a full width at half maximum (fwhm) of &gt;0.42 ?^–1 for the first sharp X-ray diffraction peak. Proper phase labeling is important for future machine learning efforts. We demonstrate that the fwhm and corrosion resistance are correlated but that, while chemistry still plays a role in corrosion resistance, a large fwhm, attributed to a glassy phase, is necessary for the highest corrosion resistance.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.9b00215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"823231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaffolding-Induced Property Modulation of Chemical Space","authors":"Jingyao Li,&nbsp;Vincenzo Di Lorenzo,&nbsp;Pravin Patil,&nbsp;Angel J. Ruiz-Moreno,&nbsp;Katarzyna Kurpiewska,&nbsp;Justyna Kalinowska-Tłuścik,&nbsp;Marco A. Velasco-Velázquez,&nbsp;Alexander Dömling*","doi":"10.1021/acscombsci.0c00072","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00072","url":null,"abstract":"<p >Physicochemical property switching of chemical space is of great importance for optimization of compounds, for example, for biological activity. Cyclization is a key method to control 3D and other properties. A two-step approach, which involves a multicomponent reaction followed by cyclization, is reported to achieve the transition from basic moieties to charge neutral cyclic derivatives. A series of multisubstituted oxazolidinones, oxazinanones, and oxazepanones as well as their thio and sulfur derivatives are synthesized from readily available building blocks with mild conditions and high yields. Like a few other methods, MCR and cyclization allow for the collective transformation of a large chemical space into a related one with different properties.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1082421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical Screening of Metallic Oxygen Reduction Reaction Catalyst Thin Films Using Getter Cosputtering","authors":"Abigail R. Van Wassen,&nbsp;Marc J. Murphy,&nbsp;Andrés Molina Villarino,&nbsp;Cara N. Gannett,&nbsp;R. Bruce van Dover,&nbsp;Héctor D. Abruña*","doi":"10.1021/acscombsci.0c00005","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00005","url":null,"abstract":"<p >Current commercial fuel cells operate in acidic media where Pt-containing compositions have been shown to be the best oxygen reduction reaction (ORR) electrocatalysts, due to their facile reaction kinetics and long-term stability under operating conditions. However, with the development of alkaline membranes, alkaline fuel cells have become a potentially viable alternative that offers the possibility of using Pt-free (precious metal-free) electrocatalysts. However, the search for better electrocatalysts can be very effort-consuming, if we intend to test every potential bi- or trimetallic combination. In this work, we have explored the application of physical vapor deposition using a custom-built getter cosputtering chamber to prepare catalyst thin films on glassy carbon electrodes, enabling catalyst compositions to be screened in a combinatorial fashion. The activity of combinations containing Au, Cu, Ag, Rh, and Pd as binary metal catalysts, in alkaline media, was studied using rotating disk electrode (RDE) voltammetry with an exchangeable disk electrode holder. Subsequently, we investigated a composition gradient of Pd–Cu, the best performing bimetallic catalyst thin film identified in the initial screening tests. Our results show the viability of using metal getter cosputtering as a rapid and effective tool for preliminary testing of ORR fuel cell electrocatalysts.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"559142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct, Competitive Comparison of Linear, Monocyclic, and Bicyclic Libraries Using mRNA Display","authors":"David E. Hacker,&nbsp;Nicolas A. Abrigo,&nbsp;Jan Hoinka,&nbsp;Stacie L. Richardson,&nbsp;Teresa M. Przytycka,&nbsp;Matthew C. T. Hartman*","doi":"10.1021/acscombsci.0c00016","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00016","url":null,"abstract":"<p >Peptide macrocyclization is typically associated with the development of higher affinity and more protease stable protein ligands, and, as such, is an important tool in peptide drug discovery. Yet, within the context of a diverse library, does cyclization give inherent advantages over linear peptides? Here, we used mRNA display to create a peptide library of diverse ring sizes and?topologies (monocyclic, bicyclic, and linear). Several rounds of in vitro selection against streptavidin were performed and the winning peptide sequences were analyzed for their binding affinities and overall topologies. The effect of adding a protease challenge on the enrichment of various peptides was also investigated. Taken together, the selection output yields insights about the relative abundance of binders of various topologies within a structurally diverse library.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1062343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy","authors":"Bhupesh Goyal*,&nbsp;Deepti Goyal*","doi":"10.1021/acscombsci.0c00058","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00058","url":null,"abstract":"<p >A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (～82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (M^pro) or 3-chymotrypsin-like cysteine protease (3CL^pro), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, M^pro is highly conserved among various CoVs, and a mutation in M^pro is often lethal to the virus. Thus, drugs targeting the M^pro enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV M^pro represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV M^pro on its dimerization and, thus, catalytic activity. We believe that the present review will stimulate research in this less explored yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1050349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of High-Throughput Methods for Sodium-Ion Battery Cathodes","authors":"Tham Adhikari,&nbsp;Alex Hebert,&nbsp;Michel Adamič,&nbsp;Jacqueline Yao,&nbsp;Karlie Potts,&nbsp;Eric McCalla*","doi":"10.1021/acscombsci.9b00181","DOIUrl":"https://doi.org/10.1021/acscombsci.9b00181","url":null,"abstract":"<p >Combinatorial synthesis of Li-ion batteries has proven extremely powerful in screening complex compositional spaces for next-generation materials. To date, no Na-ion counterpart exists wherein Na-ion cathodes can be synthesized in such a way to be comparable to that obtained in bulk synthesis. Herein, we develop a synthesis route wherein hundreds of milligram-scale powder samples can be made in a total time of 3 days. We focus on materials in the Na–Fe–Mn–O pseudoternary system of high immediate interest. Using a sol–gel method, developed herein, yields both phase-pure combinatorial samples of Na_2/3Fe_1/2Mn_1/2O₂ and NaFe_1/2Mn_1/2O₂, consistent with previous reports on bulk samples of interest commercially. By contrast, the synthesis route used for Li-ion cathodes (namely coprecipitations) does not yield phase pure materials, suggesting that the sol–gel method is more effective in mixing the Na, Fe, and Mn than coprecipitation. This has important consequences for all attempts to make these materials, even in bulk. Finally, we demonstrate that these milligram-scale powder samples can be tested electrochemically in a combinatorial cell. The resulting cyclic voltammograms are in excellent agreement with those found on bulk samples in the literature. This demonstrates that the methodology developed here will be effective in characterizing the hundreds of samples needed to understand the complex ternary systems of interest and that such results will scale-up well to the gram and kilogram scale.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.9b00181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1119485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}