ACS Combinatorial Science最新文献_第4页

Development of an Aptamer-Based Lateral Flow Assay for the Detection of C-Reactive Protein Using Microarray Technology as a Prescreening Platform 利用微阵列技术作为预筛选平台，开发一种基于适体体的检测c反应蛋白的横向流动试验

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-09-07 DOI: 10.1021/acscombsci.0c00080

Ngoc Linh Phung, Johanna G. Walter, Rebecca Jonczyk, Lisa K. Seiler, Thomas Scheper, Cornelia Blume*

{"title":"Development of an Aptamer-Based Lateral Flow Assay for the Detection of C-Reactive Protein Using Microarray Technology as a Prescreening Platform","authors":"Ngoc Linh Phung, Johanna G. Walter, Rebecca Jonczyk, Lisa K. Seiler, Thomas Scheper, Cornelia Blume*","doi":"10.1021/acscombsci.0c00080","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00080","url":null,"abstract":"For improved cost-effectiveness and temperature-stability, a ready to use lateral flow assay (LFA) is developed in this work for detecting inflammation/infection biomarker C-reactive protein (CRP) in human patient samples on the basis of aptamers. In prescreening investigations, an aptamer with CRP affinity was immobilized on microarray chips in forward and sandwich formats to optimize assay conditions. We suggest these microarray techniques as a resource-sparing and fast-screening instrument for evaluation of various conditions. The capability of the aptamer to detect CRP was shown. Optimized assay conditions were consequently transferred to the LFA-platform. Here we could demonstrate for the first time an aptamer-based LFA for the detection of CRP in human patient samples in pathologically relevant concentrations. The cutoff for CRP detection is set at 10 mg/L, providing a distinctive “yes” (≥10 mg/L CRP) or “no” (<10 mg/L CRP) answer for the patient. The resulting aptamer-based LFA is promising with regard to its application as point-of-care testing (POCT) for efficient monitoring, especially of patients affected by frequent infections or inflammations.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1461486","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}

引用次数: 14

Rapid Synthesis of a Natural Product-Inspired Uridine Containing Library 一个天然产物启发的含尿苷文库的快速合成

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-24 DOI: 10.1021/acscombsci.0c00011

Wei-Chieh Cheng*, Wan-Ju Liu, Kung-Hsiang Hu, Yee-Ling Tan, Yan-Ting Lin, Wei-An Chen, Lee-Chiang Lo*

引用次数: 0

Diversity-Oriented Synthesis of Thiazolidine-2-imines via Microwave-Assisted One-Pot, Telescopic Approach and Its Interaction with Biomacromolecules 微波辅助一锅法合成噻唑烷-2-亚胺及其与生物大分子的相互作用

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-21 DOI: 10.1021/acscombsci.0c00083

Ananya Anubhav Saikia, Ramdas Nishanth Rao, Barnali Maiti, Musuvathi Motilal Balamurali*, Kaushik Chanda*

{"title":"Diversity-Oriented Synthesis of Thiazolidine-2-imines via Microwave-Assisted One-Pot, Telescopic Approach and Its Interaction with Biomacromolecules","authors":"Ananya Anubhav Saikia, Ramdas Nishanth Rao, Barnali Maiti, Musuvathi Motilal Balamurali*, Kaushik Chanda*","doi":"10.1021/acscombsci.0c00083","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00083","url":null,"abstract":"In this work, a one-pot, telescopic approach is described for the combinatorial library of thiazolidine-2-imines. The synthetic manipulation proceeds smoothly via the reaction of 2-aminopyridine/pyrazine/pyrimidine with substituted isothiocyanates followed by base catalyzed ring closure with 1,2-dibromoethane to obtain thiazolidine-2-imines with broad substrate scope and high functional group tolerance. The synthetic strategy merges well with the thiourea formation followed by base catalyzed ring closure reaction for the thiazolidine-2-imine synthesis in a more modular and straightforward approach. The synthetic procedure reported herein represents a cleaner route toward thiazolidine-2-imines as compared to traditional methodologies. Moreover, the biological significance of combinatorially synthesized thiazolidin-2-imines has been investigated for their use as possible inhibitors for acetyl cholinesterase through molecular docking studies.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"191715","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}

引用次数: 6

MoS2–Calix[4]arene Catalyzed Synthesis and Molecular Docking Study of 2,4,5-Trisubstituted Imidazoles As Potent Inhibitors of Mycobacterium tuberculosis 二硫化钼-杯[4]芳烃催化下2,4,5-三取代咪唑的合成及分子对接研究

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-18 DOI: 10.1021/acscombsci.0c00038

Madihalli S. Raghu, Chikkur B. Pradeep Kumar, Kodalapura N. Nagendra Prasad, Maralekere K. Prashanth*, Yogesh K. Kumarswamy, Sunkara Chandrasekhar, Bantal Veeresh

{"title":"MoS2–Calix[4]arene Catalyzed Synthesis and Molecular Docking Study of 2,4,5-Trisubstituted Imidazoles As Potent Inhibitors of Mycobacterium tuberculosis","authors":"Madihalli S. Raghu, Chikkur B. Pradeep Kumar, Kodalapura N. Nagendra Prasad, Maralekere K. Prashanth*, Yogesh K. Kumarswamy, Sunkara Chandrasekhar, Bantal Veeresh","doi":"10.1021/acscombsci.0c00038","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00038","url":null,"abstract":"A MoS2-supported-calix[4]arene (MoS2-CA4) nanocatalyst was used for efficient synthesis of 2,4,5-trisubstituted imidazole derivatives from 1-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione, aldehydes and ammonium acetate under solvent-free conditions. Reusability of the catalyst up to five cycles without any significant loss in the yields of the product is the unique feature of this heterogeneous solid catalysis. Furthermore, the noteworthy highlights of this method are safe reaction profiles, broad substrate scope, excellent yields, economical, solvent-free, and simple workup conditions. All synthesized compounds were evaluated for their in vitro antitubercular (TB) activity against Mycobacterium tuberculosis (Mtb) H37Rv. Among the screened compounds 3c, 3d, 3f, 3m, and 3r had MIC values of 2.15, 2.78, 5.75, 1.36, and 0.75 μM, respectively, and exhibited more potency than the reference drugs pyrazinamide (MIC: 3.12 μM), ciprofloxacin (MIC: 4.73 μM), and ethambutol (7.61 μM). Besides, potent compounds (3c, 3d, 3f, 3m, and 3r) have been tested for inhibition of MabA (β-ketoacyl-ACP reductase) enzyme and cytotoxic activity against mammalian Vero cell line. A molecular docking study was carried out on the MabA (PDB ID: 1UZN) enzyme to predict the interactions of the synthesized compounds. The results of the in vitro anti-TB activity and docking study showed that synthesized compounds have a strong anti-TB activity and can be adapted and produced more effectively as a lead compound.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"179929","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}

引用次数: 24

Multiplexed Enzyme Activity-Based Probe Display via Hybridization 基于多路酶活性的杂交探针显示

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-17 DOI: 10.1021/acscombsci.0c00116

Valerie Cavett, Brian M. Paegel*

{"title":"Multiplexed Enzyme Activity-Based Probe Display via Hybridization","authors":"Valerie Cavett, Brian M. Paegel*","doi":"10.1021/acscombsci.0c00116","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00116","url":null,"abstract":"Emulsions offer the means to miniaturize and parallelize high-throughput screening but require a robust method to localize activity-based fluorescent probes in each droplet. Multiplexing probes in droplets is impractical, though highly desirable for identifying library members that possess very specific activity. Here, we present multiplexed probe immobilization on library beads for emulsion screening. During library bead preparation, we quantitated ～106 primers per bead by fluorescence in situ hybridization, however emulsion PCR yielded only ～103 gene copies per bead. We leveraged the unextended bead-bound primers to hybridize complementary probe-oligonucleotide heteroconjugates to the library beads. The probe-hybridized bead libraries were then used to program emulsion in vitro transcription/translation reactions and analyzed by FACS to perform multiplexed activity-based screening of trypsin and chymotrypsin mutant libraries for novel proteolytic specificity. The approach’s modularity should permit a high degree of probe multiplexing and appears extensible to other enzyme classes and library types.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"176929","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}

引用次数: 1

Dielectrophoretic Manipulation of Cancer Cells and Their Electrical Characterization 介电法处理癌细胞及其电学特性

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-06 DOI: 10.1021/acscombsci.0c00109

Ina Turcan, Marius Andrei Olariu*

{"title":"Dielectrophoretic Manipulation of Cancer Cells and Their Electrical Characterization","authors":"Ina Turcan, Marius Andrei Olariu*","doi":"10.1021/acscombsci.0c00109","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00109","url":null,"abstract":"Electromanipulation and electrical characterization of cancerous cells is becoming a topic of high interest as the results reported to date demonstrate a good differentiation among various types of cells from an electrical viewpoint. Dielectrophoresis and broadband dielectric spectroscopy are complementary tools for sorting, identification, and characterization of malignant cells and were successfully used on both primary tumor cells and culture cells as well. However, the literature is presenting a plethora of studies with respect to electrical evaluation of these type of cells, and this review is reporting a collection of information regarding the functioning principles of different types of dielectrophoresis setups, theory of cancer cell polarization, and electrical investigation (including here the polarization mechanisms). The interpretation of electrical characteristics against frequency is discussed with respect to interfacial/Maxwell–Wagner polarization and the parasitic influence of electrode polarization. Moreover, the electrical equivalent circuits specific to biological cells polarizations are discussed for a good understanding of the cells’ morphology influence. The review also focuses on advantages of specific low-conductivity buffers employed currently for improving the efficiency of dielectrophoresis and provides a set of synthesized data from the literature highlighting clear differentiation between the crossover frequencies of different cancerous cells.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"233788","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}

引用次数: 33

Considerations for Achieving Maximized DNA Recovery in Solid-Phase DNA-Encoded Library Synthesis 在固相DNA编码文库合成中实现最大DNA回收率的考虑

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-06 DOI: 10.1021/acscombsci.0c00101

Alexander K. Price*, Brian M. Paegel*

{"title":"Considerations for Achieving Maximized DNA Recovery in Solid-Phase DNA-Encoded Library Synthesis","authors":"Alexander K. Price*, Brian M. Paegel*","doi":"10.1021/acscombsci.0c00101","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00101","url":null,"abstract":"DNA-encoded library (DEL) technology enables rapid, economical synthesis, and exploration of novel chemical space. Reaction development for DEL synthesis has recently accelerated in pace with a specific emphasis on ensuring that the reaction does not compromise the integrity of the encoding DNA. However, the factors that contribute to a reaction’s “DNA compatibility” remain relatively unknown. We investigated several solid-phase reactions and encoding conditions and determined their impact on DNA compatibility. Conditions that minimized the accessibility of reactive groups on the DNA encoding tag (switching solvent, low temperature, double-stranded encoding tag) significantly improved compatibility. We showcased this approach in the multistep synthesis of an acyldepsipeptide (ADEP1) fragment, which preserved 73% of DNA for a >100-fold improvement over canonical conditions. These results are particularly encouraging in the context of multistep reaction sequences to access natural product-like scaffolds and more broadly underscore the importance of reconciling the biophysical properties and reactivity of DNA with chemistry development to yield high-quality libraries of those scaffolds.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"233793","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}

引用次数: 0

Prospects and Therapeutic Applications of Cardiac Glycosides in Cancer Remediation 心脏糖苷在癌症修复中的应用前景

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-05 DOI: 10.1021/acscombsci.0c00082

Jude I. Ayogu*, Amaechi S. Odoh*

引用次数: 15

Combinatorial Exploration and Mapping of Phase Transformation in a Ni–Ti–Co Thin Film Library Ni-Ti-Co薄膜库相变的组合探索与映射

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-04 DOI: 10.1021/acscombsci.0c00097

Naila M. Al Hasan, Huilong Hou, Tieren Gao, Jonathan Counsell, Suchismita Sarker, Sigurd Thienhaus, Edward Walton, Peer Decker, Apurva Mehta, Alfred Ludwig, Ichiro Takeuchi*

{"title":"Combinatorial Exploration and Mapping of Phase Transformation in a Ni–Ti–Co Thin Film Library","authors":"Naila M. Al Hasan, Huilong Hou, Tieren Gao, Jonathan Counsell, Suchismita Sarker, Sigurd Thienhaus, Edward Walton, Peer Decker, Apurva Mehta, Alfred Ludwig, Ichiro Takeuchi*","doi":"10.1021/acscombsci.0c00097","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00097","url":null,"abstract":"Combinatorial synthesis and high-throughput characterization of a Ni–Ti–Co thin film materials library are reported for exploration of reversible martensitic transformation. The library was prepared by magnetron co-sputtering, annealed in vacuum at 500 °C without atmospheric exposure, and evaluated for shape memory behavior as an indicator of transformation. Composition, structure, and transformation behavior of the 177 pads in the library were characterized using high-throughput wavelength dispersive spectroscopy (WDS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and four-point probe temperature-dependent resistance (R(T)) measurements. A new, expanded composition space having phase transformation with low thermal hysteresis and Co > 10 at. % is found. Unsupervised machine learning methods of hierarchical clustering were employed to streamline data processing of the large XRD and XPS data sets. Through cluster analysis of XRD data, we identified and mapped the constituent structural phases. Composition–structure–property maps for the ternary system are made to correlate the functional properties to the local microstructure and composition of the Ni–Ti–Co thin film library.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"229107","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}

引用次数: 10

Isolation of Chemically Cyclized Peptide Binders Using Yeast Surface Display 酵母表面显示法分离化学环化肽结合物

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2020-08-03 DOI: 10.1021/acscombsci.0c00076

Kaitlyn Bacon, Abigail Blain, Matthew Burroughs, Nikki McArthrur, Balaji M. Rao*, Stefano Menegatti*

{"title":"Isolation of Chemically Cyclized Peptide Binders Using Yeast Surface Display","authors":"Kaitlyn Bacon, Abigail Blain, Matthew Burroughs, Nikki McArthrur, Balaji M. Rao*, Stefano Menegatti*","doi":"10.1021/acscombsci.0c00076","DOIUrl":"https://doi.org/10.1021/acscombsci.0c00076","url":null,"abstract":"Cyclic peptides with engineered protein-binding activity have gained increasing attention for use in therapeutic and biotechnology applications. We describe the efficient isolation and characterization of cyclic peptide binders from genetically encoded combinatorial libraries using yeast surface display. Here, peptide cyclization is achieved by disuccinimidyl glutarate-mediated cross-linking of amine groups within a linear peptide sequence that is expressed as a yeast cell surface fusion. Using this approach, we first screened a library of cyclic heptapeptides using magnetic selection, followed by fluorescence activated cell sorting (FACS) to isolate binders for a model target (lysozyme) with low micromolar binding affinity (KD ～ 1.2–3.7 μM). The isolated peptides bind lysozyme selectively and only when cyclized. Importantly, we showed that yeast surface displayed cyclic peptides can be used to efficiently obtain quantitative estimates of binding affinity, circumventing the need for chemical synthesis of the selected peptides. Subsequently, to demonstrate broader applicability of our approach, we isolated cyclic heptapeptides that bind human interleukin-17 (IL-17) using yeast-displayed IL-17 as a target for magnetic selection, followed by FACS using recombinant IL-17. Molecular docking simulations and follow-up experimental analyses identified a candidate cyclic peptide that likely binds IL-17 in its receptor binding region with moderate apparent affinity (KD ～ 300 nM). Taken together, our results show that yeast surface display can be used to efficiently isolate and characterize cyclic peptides generated by chemical modification from combinatorial libraries.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":null,"pages":null},"PeriodicalIF":3.784,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1021/acscombsci.0c00076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"216099","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}

引用次数: 6