750 results match your criteria Acs Combinatorial Science[Journal]


Polymer Microarrays for the Discovery and Optimization of Robust Optical-Fiber-Based pH Sensors.

ACS Comb Sci 2019 Apr 19. Epub 2019 Apr 19.

School of Chemsitry, EaStCHEM , University of Edinburgh , King's Buildings, West Mains Road , Edinburgh EH9 3FJ , United Kingdom.

Polymer microarrays were utilized for the high-throughput screening and discovery of optimal polymeric substrates capable of trapping functional ratiometric fluorescence-based pH sensors. This led to the identification of poly(methyl methacrylate- co-2-(dimethylamino) ethyl acrylate) (PA101), which allowed, via dip coating, the attachment of fluorescent pH sensors onto the tips of optical fibers, resulting in robust, rapid, and reproducible sensing of physiological pHs. Read More

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http://dx.doi.org/10.1021/acscombsci.9b00031DOI Listing

Synthesis of Benz-Fused Azoles via C-Heteroatom Coupling Reactions Catalyzed by Cu(I) in the Presence of Glycosyltriazole Ligands.

ACS Comb Sci 2019 Apr 16. Epub 2019 Apr 16.

Department of Chemistry, Institute of Science , Banaras Hindu University , Varanasi - 221005 , India.

Glycosyl triazoles are conveniently accessible and contain multiple metal-binding units that may assist in metal-mediated catalysis. Azide derivatives of d-glucose have been converted to their respective aryltriazoles and screened as ligands for the synthesis of 2-substituted benz-fused azoles and benzimidazoquinazolinones by Cu-catalyzed intramolecular Ullmann type C-heteroatom coupling. Good to excellent yields for a variety of benz-fused heterocyles were obtained for this readily accessible catalytic system. Read More

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http://dx.doi.org/10.1021/acscombsci.9b00004DOI Listing

On the Early Years of High Throughput Experimentation and Combinatorial Approaches in Catalysis and Materials Science.

Authors:
Wilhelm Maier

ACS Comb Sci 2019 Apr 2. Epub 2019 Apr 2.

A report on the early years of combinatorial materials science and technology. High throughput technologies HTT are found in life science and materials laboratories. While in life sciences HTT became long standard for academia as well as industry, HTT in materials became standard in industry, but not in academia. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00189DOI Listing
April 2019
1 Read

Intramolecular Electrophilic Cyclization Approach to 6-Substituted Naphtho[2,1- b]benzofurans: Novel Dual-State Emissive Fluorophores with Blue Emission.

ACS Comb Sci 2019 Apr 9. Epub 2019 Apr 9.

College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences , Yonsei University , 85 Songdogwahak-ro, Yeonsu-gu , Incheon 21983 , Republic of Korea.

A regiospecific synthesis of naphtho[2,1- b]benzofurans with a substituent at the C6 position was achieved via intramolecular 6-endo-dig electrophilic cyclization under acidic conditions to construct the central aromatic C ring. Screening of the synthesized compounds using a high-content imaging system enabled us to discover novel dual state emissive compounds 2{ 1,6}, 2{ 1,8}, and 2{ 4,3}, which are highly emissive with blue emission in their solid states as well as in solution states in most solvents. In addition, the compounds 2{ 4,3}, 2{ 4,12}, and 2{ 5,13} were found to be the most cell permeable in HeLa cells for live cell imaging with negligible phototoxicity. Read More

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http://dx.doi.org/10.1021/acscombsci.9b00006DOI Listing

Polymerase-Extension-Based Selection Method for DNA-Encoded Chemical Libraries against Nonimmobilized Protein Targets.

ACS Comb Sci 2019 Apr 1. Epub 2019 Apr 1.

Department of Chemistry , The University of Hong Kong , Pokfulam Road , Hong Kong SAR , China.

DNA-encoded chemical libraries (DELs) have become an important ligand discovery technology in biomedical research and drug discovery. DELs can be comprised of hundreds of millions to billions of candidate molecules and provide outstanding chemical diversity for discovering novel ligands and inhibitors for a large variety of biological targets. However, in most cases, DELs are selected against purified and immobilized proteins based on binding affinity. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.9b00011
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http://dx.doi.org/10.1021/acscombsci.9b00011DOI Listing
April 2019
6 Reads

Optimization of the Anodization Processing for Aluminum Oxide Gate Dielectrics in ZnO Thin Film Transistors by Multivariate Analysis.

ACS Comb Sci 2019 Mar 28. Epub 2019 Mar 28.

School of Electronic Engineering , Bangor University , LL57 2DG Bangor , Gwynedd , Wales, U.K.

The present study reports a two-level multivariate analysis to optimize the production of anodized aluminum oxide (AlO) dielectric films for zinc oxide thin-film transistors (TFTs). Fourteen performance parameters were measured and analysis of variance (ANOVA) of the combined responses has been applied to identify how the AlO dielectric fabrication process influences the electrical properties of the TFTs. Using this approach, the levels for the manufacturing factors to achieve optimal overall device performance have been identified and ranked. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00195
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http://dx.doi.org/10.1021/acscombsci.8b00195DOI Listing
March 2019
8 Reads

An Inter-Laboratory Study of Zn-Sn-Ti-O Thin Films using High-throughput Experimental Methods.

ACS Comb Sci 2019 Mar 19. Epub 2019 Mar 19.

High-throughput experimental (HTE) techniques are an increasingly important way to accelerate the rate of materials research and development for many technological applications. However, there are very few publications on the reproducibility of the HTE results obtained across different laboratories for the same materials system, and on the associated sample and data exchange standards. Here, we report a comparative study of Zn-Sn-Ti-O thin films materials using high-throughput experimental methods at National Institute of Standards and Technology (NIST) and National Renewable Energy Laboratory (NREL). Read More

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http://dx.doi.org/10.1021/acscombsci.8b00158DOI Listing

Activity-Based DNA-Encoded Library Screening.

ACS Comb Sci 2019 Mar 29. Epub 2019 Mar 29.

Roche Pharma Research and Early Development (pRED) Roche Innovation Center Basel F. Hoffman-La Roche Ltd Grenzacherstrasse 124 CH-4070 Basel Switzerland.

Robotic high-throughput compound screening (HTS) and, increasingly, DNA-encoded library (DEL) screening are driving bioactive chemical matter discovery in the postgenomic era. HTS enables activity-based investigation of highly complex targets using static compound libraries. Conversely, DEL grants efficient access to novel chemical diversity, although screening is limited to affinity-based selections. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.9b00037
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http://dx.doi.org/10.1021/acscombsci.9b00037DOI Listing
March 2019
11 Reads

Synthesis of 2-Amino-5-Carboxamide Thiazole Derivatives via Dehydrative Cyclization of Thiourea Intermediate Resin on Solid Phase.

ACS Comb Sci 2019 Mar 20. Epub 2019 Mar 20.

Innovative Drug Library Research Center, Department of Chemistry, College of Science , Dongguk University , 30, Pildong-ro 1-gil , Jung-gu, Seoul 04620 , Korea.

In this study, we synthesized 2-amino-5-carboxamide thiazole derivatives on solid phase. The synthesis of the library starts with the reductive amination of the 4-formyl-3-methoxy phenoxy resin to prevent isomer formation. The dehydrative cyclization of thiourea intermediate resin, which is the key step in the synthetic process, was successfully synthesized using α-bromoketone in the presence of the DMF so as to afford 2-amino-5-carboxylate thiazole resin. Read More

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http://dx.doi.org/10.1021/acscombsci.9b00001DOI Listing

Development of a High-Throughput Screening Method for Oxide-Ion Conductors and Its Application to Bismuth-Based Oxide Library Thin Films.

ACS Comb Sci 2019 Mar 18. Epub 2019 Mar 18.

Toyota Central R&D Laboratories, Inc. , Nagakute , Aichi 480-1192 , Japan.

To accelerate material discovery, we develop a screening method for oxide-ion conductors that comprises combinatorial synthesis using chemical-solution deposition and high-throughput measurements using X-ray diffraction and conductivity. The present method allows us to form an arbitrary and uniform composition within an evaluation area at an arbitrary position in the library on a substrate. This screening method is applied to ABiZr (NbTa )O bismuth-layered compounds, which are known to have relatively high oxide-ion conductivities but are yet to be examined thoroughly. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00193DOI Listing
March 2019
6 Reads

Enantioselective Synthesis of Hydantoin and Diketopiperazine-Fused Tetrahydroisoquinolines via Pictet-Spengler Reaction.

ACS Comb Sci 2019 Apr 6;21(4):336-344. Epub 2019 Mar 6.

Department of Applied Chemistry , National Chiao-Tung University , Hsinchu 300 , Taiwan.

An enantioselective synthesis of iso-, isothio-, and isoselenohydantoin and diketopiperazine-fused tetrahydroisoquinolines from l-Dopa was reported. The route consists of an Pictet-Spengler reaction of ( S)-2-amino-3-(3,4-dimethoxyphenyl)propanoates with various aldehydes to afford diastereomeric tetrahydroisoquinolines. Next step, the tetrahydroisoquinolines were further reacted with iso-, isothio-, or isoselenocyanates to construct hydantoin. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.9b00005
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http://dx.doi.org/10.1021/acscombsci.9b00005DOI Listing
April 2019
2 Reads

Structural and Functional Properties of the Thin Film System Ti-Ni-Si.

ACS Comb Sci 2019 Mar 14. Epub 2019 Mar 14.

Chair for MEMS Materials, Institute for Materials, Faculty of Mechanical Engineering , Ruhr University Bochum , Universitaetsstrasse 150 , D-44801 Bochum , Germany.

The thin film system Ti-Ni-Si was investigated using methods of combinatorial materials science. A thin film composition spread library of the system was fabricated using combinatorial magnetron sputtering. The functional properties Seebeck coefficient, electrical resistivity, and luminance were determined using high-throughput characterization techniques. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00181DOI Listing
March 2019
2 Reads

Analysis of CH Uptake over Metal-Organic Frameworks Using Data-Mining Tools.

ACS Comb Sci 2019 Apr 13;21(4):257-268. Epub 2019 Mar 13.

Department of Chemical Engineering , Bogazici University , Bebek , Besiktas, 34342 Istanbul , Turkey.

A database containing 2224 data points for CH storage or delivery in metal-organic frameworks (MOFs) was analyzed using machine-learning tools to extract knowledge for generalization. The database was first reviewed to observe the basic trends and patterns. It was then analyzed using decision trees and artificial neural networks (ANN) to extract hidden information and develop rules and heuristics for future studies. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00150DOI Listing
April 2019
1 Read

Electrochemical screening of tungsten trioxide - nickel oxide thin film combinatorial library at low nickel concentrations.

ACS Comb Sci 2019 Feb 27. Epub 2019 Feb 27.

The electrochemical behavior of a tungsten trioxide-nickel oxide (WO-NiO) thin film library was investigated using scanning droplet cell microscopy (SDCM) in 0.1 mol dm sodium perchlorate (NaClO) solution. The WO-Ni film library was deposited by thermal co-evaporation on an indium tin oxide (ITO)-coated glass substrate in an atomic Ni concentration range from 2. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00117DOI Listing
February 2019
3 Reads

Dynamical Correlations for Statistical Copolymers from High-Throughput Broad-Band Dielectric Spectroscopy.

ACS Comb Sci 2019 Apr 22;21(4):276-299. Epub 2019 Feb 22.

Department of Chemical and Biomedical Engineering , University of South Florida , Tampa , Florida 33620 , United States.

Broad-band dielectric spectroscopy (BDS) provides a powerful method of characterizing relaxation dynamics in diverse materials. Here we describe and employ a novel instrument for high-throughput broad-band dielectric spectroscopy (HTBDS) that accelerates this capability, enabling simultaneous measurements of 48 samples. This capability is based around a coaxial switching system for rapid scanning between multiple samples on the same sample stage, coordinated with shared environmental control. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00160DOI Listing
April 2019
1 Read

Electrical and Structural Properties of the Partial Ternary Thin-Film System Ni-Si-B.

ACS Comb Sci 2019 Apr 11;21(4):310-315. Epub 2019 Mar 11.

Chair of MEMS Materials, Institute for Materials, Faculty of Mechanical Engineering , Ruhr-University Bochum , Universitaetsstrasse 150 , D-44801 Bochum , Germany.

High-throughput and combinatorial materials science methods were used to investigate the dependence of the work function in the Ni-Si system on the B content (0-30 at. %). Alloying of NiSi is used to adapt its properties to suit the needs as a gate electrode material. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00175DOI Listing
April 2019
1 Read

Base Controlled Three-Component Regioselective Synthesis of 2-Imino Thiazolines and 2-Thioxoimidazolin-4-ones.

ACS Comb Sci 2019 Apr 18;21(4):269-275. Epub 2019 Feb 18.

Department of Applied Chemistry , National Chiao-Tung University , 1001 Ta-Hseuh Road , Hsinchu 300-10 , Taiwan.

Base-controlled regioselective synthesis of 2-imino thiazolines and 2-thioxoimidazolin-4-ones was achieved to use a one-pot reaction between chiral amino esters, isothiocyanates, and α-bromoketones/alkyl halides. This three-component coupling reaction in acetonitrile provides 2-imino thiazolines, whereas the formation of 2-thioxoimidazolin-4-ones was observed under basic conditions at ambient temperature. The corresponding products were obtained in good to excellent yield with broad substrate scope. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00152DOI Listing
April 2019
1 Read

Biophysical Characterization Platform Informs Protein Scaffold Evolvability.

ACS Comb Sci 2019 Apr 18;21(4):323-335. Epub 2019 Feb 18.

Department of Chemical Engineering and Materials Science , University of Minnesota-Twin Cities , 421 Washington Avenue Southeast, 356 Amundson Hall , Minneapolis , Minnesota 55455 , United States.

Evolving specific molecular recognition function of proteins requires strategic navigation of a complex mutational landscape. Protein scaffolds aid evolution via a conserved platform on which a modular paratope can be evolved to alter binding specificity. Although numerous protein scaffolds have been discovered, the underlying properties that permit binding evolution remain unknown. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00182
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http://dx.doi.org/10.1021/acscombsci.8b00182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458986PMC
April 2019
11 Reads

Development of a Method To Prioritize Protein-Ligand Pairs on Beads Using Protein Conjugated to a Near-IR Dye.

ACS Comb Sci 2019 Mar 1;21(3):223-228. Epub 2019 Feb 1.

Department of Medicinal Chemistry and Molecular Pharmacology , Purdue University , 575 West Stadium Avenue , West Lafayette , Indiana 47907 , United States.

The development of techniques to screen one-bead-one-compound (OBOC) libraries remains a critical step in identifying small molecules that bind target proteins. While great strides have been made, there remains a need to continue to develop OBOC screening techniques that not only reliably identify hit molecules but also can distinguish poor from excellent binders in a single screen. Similarly, relatively strong binding between a small molecule and protein target is required to be considered a hit from the initial pool of screened molecules. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00165DOI Listing

High-Throughput Screening of the Alkoxide/Oxime-Based Library: An Alternative to Organotin Compounds for the Alkoxysilane Condensation in Adhesives and Sealants.

ACS Comb Sci 2019 Apr 6;21(4):300-309. Epub 2019 Feb 6.

Total S.A. , Tour Michelet A, 24, Cours Michelet , 92069 Cedex La Défense , France.

In this work, a high-throughput screening (HTS) method was used to discover new efficient catalysts to substitute organotin compounds (DBTDL) for the cross-linking of silyl-modified polymers (SMPs). We report here on the use of our HTS method to investigate a library of alkoxide/oxime systems with different metal/ligand (M/L) ratios. Among the 156 candidates tested, 40 interesting hits were detected. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00161DOI Listing
April 2019
1 Read

Novel Cellularly Active Inhibitor Regresses DDAH1 Induced Prostate Tumor Growth by Restraining Tumor Angiogenesis through Targeting DDAH1/ADMA/NOS Pathway.

ACS Comb Sci 2019 Apr 7;21(4):241-256. Epub 2019 Feb 7.

Applied Biology , Indian Institute of Chemical Technology (CSIR-IICT) , Hyderabad , India.

Dimethylarginine dimethylaminohydrolase1 (DDAH1) inhibitors are important therapeutics by virtue of their ability to control nitric oxide (NO) production by elevating asymmetric dimethylarginine (ADMA) levels. In a screening campaign, we identified that DD1E5 (3-amino-6- tert-butyl-N-(1,3-thiazol-2-yl)-4-(trifluoromethyl)thieno[2,3- b]pyridine-2- carboxamide) inhibits the DDAH1 activity both in vitro and in cultured cells. Mechanistic studies found that DD1E5 is a competitive inhibitor (dissociation constant ( K) of 2. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00133DOI Listing
April 2019
12 Reads

Application of Glaser-Hay Diyne Coupling To Constrain N-Amino Acid Amides via a N-N Bridge.

ACS Comb Sci 2019 Apr 11;21(4):316-322. Epub 2019 Feb 11.

Department of Organic Chemistry, Faculty of Science , Palacky University , 17. Listopadu 12 , 771 46 Olomouc , Czech Republic.

We present the application of a Glaser-Hay diyne coupling for the synthesis of conformationally constrained N-amino acid amides with different diyne ring sizes. Twelve-membered rings were the smallest rings that could be prepared by this approach. We observed the formation of triethylammonium adducts in the cases of smaller (10- and 11-membered) rings. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00179DOI Listing
April 2019
10 Reads

Quantitative Comparison of Enrichment from DNA-Encoded Chemical Library Selections.

ACS Comb Sci 2019 Feb 23;21(2):75-82. Epub 2019 Jan 23.

FORMA Therapeutics Inc. , 500 Arsenal Street, Suite 100 , Watertown , Massachusetts 02472 , United States.

DNA-encoded chemical libraries (DELs) provide a high-throughput and cost-effective route for screening billions of unique molecules for binding affinity for diverse protein targets. Identifying candidate compounds from these libraries involves affinity selection, DNA sequencing, and measuring enrichment in a sample pool of DNA barcodes. Successful detection of potent binders is affected by many factors, including selection parameters, chemical yields, library amplification, sequencing depth, sequencing errors, library sizes, and the chosen enrichment metric. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00116
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http://dx.doi.org/10.1021/acscombsci.8b00116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372980PMC
February 2019
4 Reads

Synthesis of Aza-acyclic Nucleoside Libraries of Purine, Pyrimidine, and 1,2,4-Triazole.

ACS Comb Sci 2019 Mar 31;21(3):183-191. Epub 2019 Jan 31.

Department of Medicine, Division of Hematology and Oncology , University of Alabama at Birmingham , NP 2540 J, 1720 Second Avenue South , Birmingham , Alabama 35294-3300 , United States.

Under the aegis of the Pilot Scale Library Program of the NIH Roadmap Initiative, a new library of propan-1-amine containing aza acyclic nucleosides was designed and prepared, and we now report a diverse set of 157 purine, pyrimidine, and 1,2,4-triazole- N-acetamide analogues. These new nucleoside analogues were prepared in a parallel high throughput solution-phase format. A set of diverse amines was reacted with several nucleobase N-propaldehydes utilizing reductive amination with sodium triacetoxyborohydride coupling to produce a small and diverse aza acyclic nucleoside library. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00136DOI Listing
March 2019
6 Reads

Highly Regioselective, Acid-Catalyzed, Three-Component Cascade Reaction for the Synthesis of 2-aminopyridine-Decorated Imidazo[1,2- a]pyridine.

ACS Comb Sci 2019 Mar 22;21(3):149-153. Epub 2019 Jan 22.

School of Chemistry and Chemical Engineering and Guangdong Cosmetics Engineering & Technology Research Center , Guangdong Pharmaceutical University , Zhongshan 528458 , China.

A highly regioselective acid-catalyzed three-component reaction of 2-aminopyridine and 3-phenylpropiolaldehyde for the construction of imidazo[1,2- a]pyridine has been developed. This strategy provides a broad range of substrates and represents an efficient approach to give various 2-aminopyridine-decorated imidazo[1,2- a]pyridine in good yields. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00149DOI Listing
March 2019
1 Read

Biginelli Reaction: Polymer Supported Catalytic Approaches.

ACS Comb Sci 2019 Mar 6;21(3):105-148. Epub 2019 Feb 6.

Department of Chemistry, P.S.G.V.P.M's SIP Arts , GBP Science and STKVS Commerce College , Shahada , Nandurbar - 425409 , India.

The Biginelli product, dihydropyrimidinone (DHPM) core, and its derivatives are of immense biological importance. There are several methods reported as modifications to the original Biginelli reaction. Among them, many involve the use of different catalysts. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00120DOI Listing
March 2019
3 Reads

Polymer-Assisted Synthesis of Single and Fused Diketomorpholines.

ACS Comb Sci 2019 Mar 18;21(3):154-157. Epub 2019 Jan 18.

Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry , Palacký University , Hněvotínská 5 , 779 00 , Olomouc , Czech Republic.

The synthesis of different diketomorpholines via N-acyl-3,4-dihydro-2 H-1,4-oxazine-3-carboxylic acids is reported in this article. The key intermediates were prepared using a convenient solid-phase synthesis starting from polymer-supported Ser( tBu)-OH. After subsequent sulfonylation with 4-nitrobenzenesulfonyl chloride (4-Nos-Cl), alkylation with an α-bromoketone, cleavage of the 4-Nos group and acylation with an α-halocarboxylic acids, acid-mediated cleavage from the resin yielded dihydrooxazine-3-carboxylic acids in high crude purities. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00176DOI Listing
March 2019
1 Read

Life-Saving Threads: Advances in Textile-Based Analytical Devices.

ACS Comb Sci 2019 Apr 11;21(4):229-240. Epub 2019 Feb 11.

ARC Centre of Excellence in Electromaterials Science (ACES), AIIM Facility, Innovation Campus , University of Wollongong , New South Wales 2500 , Australia.

Novel approaches that incorporate electrofluidic and microfluidic technologies are reviewed to illustrate the translation of traditional enclosed structures into open and accessible textile based platforms. Through the utilization of on-fiber and on-textile microfluidics, it is possible to invert the typical enclosed capillary column or microfluidic "chip" platform, to achieve surface accessible efficient separations and fluid handling, while maintaining a microfluidic environment. The open fiber/textile based fluidics approach immediately provides new possibilities to interrogate, manipulate, redirect, extract, characterize, and quantify solutes and target species at any point in time during such processes as on-fiber electrodriven separations. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00126DOI Listing
April 2019
1 Read

Targeting Protein-Protein Interactions of Tyrosine Phosphatases with Microarrayed Fragment Libraries Displayed on Phosphopeptide Substrate Scaffolds.

ACS Comb Sci 2019 Mar 31;21(3):158-170. Epub 2019 Jan 31.

Molecular and Translational Sciences Division , United States Army Medical Research Institute of Infectious Diseases , Frederick , Maryland 21702 , United States.

Chemical library screening approaches that focus exclusively on catalytic events may overlook unique effects of protein-protein interactions that can be exploited for development of specific inhibitors. Phosphotyrosyl (pTyr) residues embedded in peptide motifs comprise minimal recognition elements that determine the substrate specificity of protein tyrosine phosphatases (PTPases). We incorporated aminooxy-containing amino acid residues into a 7-residue epidermal growth factor receptor (EGFR) derived phosphotyrosine-containing peptide and subjected the peptides to solution-phase oxime diversification by reacting with aldehyde-bearing druglike functionalities. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00122
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http://dx.doi.org/10.1021/acscombsci.8b00122DOI Listing
March 2019
11 Reads

Bicyclic RGD Peptides with Exquisite Selectivity for the Integrin αβ Receptor Using a "Random Design" Approach.

ACS Comb Sci 2019 Mar 26;21(3):198-206. Epub 2019 Jan 26.

Pepscan Therapeutics , Zuidersluisweg 2 , 8243 RC Lelystad , The Netherlands.

We describe the identification of bicyclic RGD peptides with high affinity and selectivity for integrin αβ via high-throughput screening of partially randomized libraries. Peptide libraries (672 different compounds) comprising the universal integrin-binding sequence Arg-Gly-Asp (RGD) in the first loop and a randomized sequence XXX (X being one of 18 canonical l-amino acids) in the second loop, both enclosed by either an l- or d-Cys residue, were converted to bicyclic peptides via reaction with 1,3,5-tris(bromomethyl)benzene (T3). Screening of first-generation libraries yielded lead bicyclic inhibitors displaying submicromolar affinities for integrin αβ (e. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00144DOI Listing
March 2019
2 Reads

Cellular-Based Selections Aid Yeast-Display Discovery of Genuine Cell-Binding Ligands: Targeting Oncology Vascular Biomarker CD276.

ACS Comb Sci 2019 Mar 24;21(3):207-222. Epub 2019 Jan 24.

Department of Chemical Engineering and Materials Science , University of Minnesota-Twin Cities , Minneapolis , Minnesota 55455 , United States.

Yeast surface display is a proven tool for the selection and evolution of ligands with novel binding activity. Selections from yeast surface display libraries against transmembrane targets are generally carried out using recombinant soluble extracellular domains. Unfortunately, these molecules may not be good models of their true, membrane-bound form for a variety of reasons. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00156
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http://dx.doi.org/10.1021/acscombsci.8b00156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411437PMC
March 2019
6 Reads

Mild and Efficient Palladium-Mediated C-N Cross-Coupling Reaction between DNA-Conjugated Aryl Bromides and Aromatic Amines.

ACS Comb Sci 2019 Feb 10;21(2):69-74. Epub 2019 Jan 10.

Centro de Investigación Lilly, S. A. , 28108 Alcobendas, Madrid , Spain.

DNA-encoded library technology (ELT) has emerged in the pharmaceutical industry as a powerful tool for hit and lead generation. Over the last 10 years, a number of DNA-compatible chemical reactions have been published and used to synthesize libraries. Among the most commonly used reactions in medicinal chemistry is the C-N bond formation, and its application to DNA-encoded library technology affords an alternative approach to identify high-affinity binders for biologically relevant protein targets. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00142DOI Listing
February 2019
6 Reads

Post-Glycosylation Diversification (PGD): An Approach for Assembling Collections of Glycosylated Small Molecules.

ACS Comb Sci 2019 Mar 15;21(3):192-197. Epub 2019 Jan 15.

Department of Chemistry , University of Connecticut , 55 N. Eagleville Road, U3060 , Storrs , Connecticut 06269 , United States.

Many small molecule natural products with antibiotic and antiproliferative activity are adorned with a carbohydrate residue as part of their molecular structure. The carbohydrate moiety can act to mediate key interactions with the target, attenuate physicochemical properties, or both. Facile incorporation of a carbohydrate group on de novo small molecules would enable these valuable properties to be leveraged in the evaluation of focused compound libraries. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00139
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http://dx.doi.org/10.1021/acscombsci.8b00139DOI Listing
March 2019
2 Reads

Chemo-Diversification of Plant Extracts Using a Generic Bromination Reaction and Monitoring by Metabolite Profiling.

ACS Comb Sci 2019 Mar 17;21(3):171-182. Epub 2019 Jan 17.

Microbiology Unit, Department of Botany and Plant Biology , University of Geneva , 30 quai Ernest-Ansermet , 1211 Geneva 4, Switzerland.

A generic procedure for direct bromination of polyphenol in crude plant extracts was developed to generate multiple "unnatural" halogenated natural products for further bioassay evaluation. To better control the halogenation procedure, the bromination was optimized with a flavonoid standard, and the reactions were monitored by high-performance liquid chromatography photometric diode array coupled to the evaporative light scattering detection (ELSD). ELSD detection was successfully used for a relative yield estimation of the compounds obtained. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00132DOI Listing
March 2019
7 Reads

Advances in the Solid-Phase Synthesis of Pyrimidine Derivatives.

ACS Comb Sci 2019 Feb 17;21(2):35-68. Epub 2019 Jan 17.

School of Chemical Sciences , Mahatma Gandhi University , Kottayam , Kerala 686560 , India.

This Review describes the existing synthetic approaches for the solid-phase synthesis (SPS) of differently substituted and fused pyrimidine derivatives. These synthetic strategies are classified on the basis of the different synthetic routes leading to the particular type of pyrimidine heterocycle formed. The Review discusses the application of a variety of polystyrene derived supports for the construction of pyrimidine rings. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00172DOI Listing
February 2019
1 Read

Exploration of Catalytic Nucleic Acids on Porphyrin Metalation and Peroxidase Activity by in Vitro Selection of Aptamers for N-Methyl Mesoporphyrin IX.

ACS Comb Sci 2019 Feb 9;21(2):83-89. Epub 2019 Jan 9.

CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics , Chinese Academy of Sciences , Suzhou 215123 , China.

To develop a novel light-up probe and DNAzyme, we selected aptamers for N-methyl mesoporphyrin IX (NMM), a common fluorogenic analogue of coenzyme hemin, by a modified affinity chromatography-based systematic evolution of ligands by exponential enrichment (SELEX). Two truncated aptamers Nm1 and Nm2 with low micromolar dissociation constants (0.75 and 13. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00129DOI Listing
February 2019
2 Reads

FTIR Spectroscopy Suggests a Revised Mode of Action for the Cationic Side-Chain Effect of Ionic Liquids.

ACS Comb Sci 2019 Feb 7;21(2):90-97. Epub 2019 Jan 7.

Functional Microbiology, Institute of Microbiology, Department of Pathobiology , University of Veterinary Medicine , Veterinaerplatz 1 , 1210 Vienna , Austria.

Over the past decades, ionic liquids (ILs) have gained considerable attention from the scientific community because of their versatile and designable properties. As a result, there are numerous IL applications, not only in organic synthesis, catalysis, or extraction but also as active pharmaceutical ingredients or novel antimicrobials. While considerable effort has been put into developing quantitative structure-activity relationship (QSAR) models for IL toxicity prediction, little is known about their actual mode of action. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00141DOI Listing
February 2019
5 Reads

Synthesis of D-Ring Annulated Pyridosteroids from β-Formyl Enamides and Their Biological Evaluations.

ACS Comb Sci 2019 Jan 2;21(1):11-27. Epub 2019 Jan 2.

Chemical Science and Technology Division , CSIR-North East Institute of Science & Technology , Jorhat , Assam , India 785006.

Herein, we report the synthesis of a novel class of substituted androst[17,16- b]pyridines (pyridosteroids) from the reaction of β-formyl enamides with alkynes in high yields. The optimized reaction protocol was extended to acyclic and cyclic β-formyl enamides to afford nonsteroidal pyridines. Cell survival assay of all compounds were carried against prostate cancer PC-3 cells wherein 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine showed the highest cytotoxic activity. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00140
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http://dx.doi.org/10.1021/acscombsci.8b00140DOI Listing
January 2019
5 Reads

Multicomponent Approach to a Library of N-Substituted γ-Lactams.

ACS Comb Sci 2019 Jan 24;21(1):28-34. Epub 2018 Dec 24.

Ruđer Bošković Institute , Division of Organic Chemistry and Biochemistry , Bijenička cesta 54 , 10000 Zagreb , Croatia.

The γ-lactam motif is often found in naturally occurring compounds with diverse biological activities. We prepared a 28-member library of N-substituted γ-lactams following a single-pot, three-component Ugi reaction comprising bifunctional building block, l-glutamic acid methyl ester. The reaction tolerates structurally diverse carbonyl and isocyanide components providing a robust access to functionalized γ-lactams. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00147DOI Listing
January 2019
1 Read

Combinatorial Peptide Microarray Synthesis Based on Microfluidic Impact Printing.

ACS Comb Sci 2019 Jan 30;21(1):6-10. Epub 2018 Dec 30.

Department of Biomedical Engineering , University of California , Davis , California 95616-5270 , United States.

In this Research Article, a novel inkjet printing technique, micro impact printing (MI printing), is applied for the first time to combinatorial peptide microarray synthesis on amine functionalized microdisc arrays through standard Fmoc chemistry. MI printing shows great advantages in combinatorial peptide microarray synthesis compared with other printing techniques, including (1) a disposable cartridge; (2) a small spot size (80 μm) increases array density; (3) minimal loading volume (0.6 μL) and dead volume (<0. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00125
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http://dx.doi.org/10.1021/acscombsci.8b00125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335607PMC
January 2019
22 Reads

Traceless Solid-Phase Synthesis of 1' H-Spiro[Pyrrolidine-3,2'-quinazolin]-2-ones and 1' H-Spiro[Piperidine-3,2'-quinazolin]-2-ones via Lactamization of 1,2-Dihydroquinazoline-2-carboxylates.

ACS Comb Sci 2019 Jan 20;21(1):1-5. Epub 2018 Dec 20.

Department of Organic Chemistry, Faculty of Science , Palacký University , 17 listopadu 12 , 771 46 Olomouc , Czech Republic.

We present the solid-phase synthesis of 1,2-dihydroquinazoline-2-carboxylate derivatives with a quaternary carbon in position 2 and their subsequent cyclization in solution into compounds with unique 3D architectures and pharmacological relevance-spiroquinazolines, namely, 1' H-spiro[pyrrolidine-3,2'-quinazolin]-2-ones and 1' H-spiro[piperidine-3,2'-quinazolin]-2-ones. Acyclic precursors were prepared from commercially available building blocks: protected amino acids (2,4-diaminobutyric acid and ornithine), 2-nitrobenzensulfonyl chlorides and α-bromoacetophenones. The crucial step of the synthesis was a base-mediated tandem reaction including C-arylation followed by cyclization into indazole oxides, and the formation of a 5-membered heterocycle was accomplished by ring expansion into quinazolines. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00145DOI Listing
January 2019
1 Read

Quantitative Single-Cell Analysis of Isolated Cancer Cells with a Microwell Array.

ACS Comb Sci 2019 Feb 13;21(2):98-104. Epub 2018 Dec 13.

Center for Biomaterials, Biomedical Research Institute , Korea Institute of Science and Technology (KIST) , 5 Hwarang-ro 14-gil , Seongbuk-gu, Seoul 02792 , Republic of Korea.

The heterogeneous nature of tumor-cell populations suggests that quantitative analysis at the single-cell level may provide better insights into cancer biology. Specifically, detection of multiple biomarkers from a single cell offers important initial information about cellular behavior. However, conventional approaches limit biomarker detection at the single-cell level. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00151DOI Listing
February 2019
3 Reads

Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents.

ACS Comb Sci 2018 Dec 29;20(12):700-721. Epub 2018 Nov 29.

N. D. Zelinsky Institute of Organic Chemistry RAS , 47 Leninsky Prospect , 119991 Moscow , Russian Federation.

A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure-activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00113
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http://dx.doi.org/10.1021/acscombsci.8b00113DOI Listing
December 2018
10 Reads

Combating a Master Manipulator: Staphylococcus aureus Immunomodulatory Molecules as Targets for Combinatorial Drug Discovery.

ACS Comb Sci 2018 Dec 8;20(12):681-693. Epub 2018 Nov 8.

Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science , Wuhan University of Technology , 205 Luoshi Road , Wuhan 430070 , Hubei , P. R. China.

Staphylococcus aureus is a bacterial pathogen that can cause significant disease burden and mortality by counteracting host defenses through producing virulence factors to survive the immune responses evoked by infection. This emerging drug-resistant pathogen has led to a decline in the efficacy of traditional antimicrobial therapy. To combat these threats, precision antimicrobial therapeutics have been created to target key virulence determinants of specific pathogens. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00088
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http://dx.doi.org/10.1021/acscombsci.8b00088DOI Listing
December 2018
16 Reads

Small Library of Triazolyl Polyphenols Correlating Antioxidant Activity and Stability with Number and Position of Hydroxyl Groups.

ACS Comb Sci 2018 Dec 2;20(12):694-699. Epub 2018 Nov 2.

Instituto de Química Médica (IQM-CSIC) , Juan de la Cierva 3 , 28006 Madrid , Spain.

Polyphenolic compounds have attracted much interest because of their antioxidant properties and multiple applications, from food or cosmetic preservatives to free radical scavengers as therapeutic agents. Inspired by common OH substitutions in natural products, here we describe a small library of 1,2,3-triazoles disubstituted with polyphenol groups at 1,4-positions, in an attempt to correlate the number and position of hydroxyl groups in the aromatic rings with the antioxidant activity. Some compounds from this library exhibit strong radical scavenging activities in the oxygen radical absorbance capacity assay, similar to or even higher than resveratrol and other well-kwon flavonoids. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00118
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http://dx.doi.org/10.1021/acscombsci.8b00118DOI Listing
December 2018
6 Reads

(Chlorosulfonyl)benzenesulfonyl Fluorides-Versatile Building Blocks for Combinatorial Chemistry: Design, Synthesis and Evaluation of a Covalent Inhibitor Library.

ACS Comb Sci 2018 Nov 1;20(11):672-680. Epub 2018 Nov 1.

National Taras Shevchenko University of Kyiv, Volodymyrska Street 60 , Kyiv 01601 , Ukraine.

Multigram synthesis of (chlorosulfonyl)benzenesulfonyl fluorides is described. Selective modification of these building blocks at the sulfonyl chloride function under parallel synthesis conditions is achieved. It is shown that the reaction scope includes the use of (hetero)aromatic and electron-poor aliphatic amines (e. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00130
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http://dx.doi.org/10.1021/acscombsci.8b00130DOI Listing
November 2018
5 Reads

High-Throughput Screening Solar-Thermal Conversion Films in a Pseudobinary (Cr, Fe, V)-(Ta, W) System.

ACS Comb Sci 2018 Nov 24;20(11):602-610. Epub 2018 Oct 24.

Beijing Advanced Innovation Center for Materials Genome Engineering , Beijing 100083 , China.

The properties and microstructure of (Cr, Fe, V)-(Ta, W) high-entropy films (HEFs) are studied using combinatorial strategies. The compositional library of (CrFeV) (TaW), (0 < x < 100), HEFs are fabricated by cosputtering to discover potential photothermal conversion materials. By verifying points in the compositional library, the structure and property variation according to the atomic content of elements are carefully studied. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00055
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http://dx.doi.org/10.1021/acscombsci.8b00055DOI Listing
November 2018
3 Reads

Combinatorial Material Science and Strain Engineering Enabled by Pulsed Laser Deposition Using Radially Segmented Targets.

ACS Comb Sci 2018 Nov 26;20(11):643-652. Epub 2018 Oct 26.

Felix Bloch Institute for Solid State Physics , Universität Leipzig , Leipzig , Germany.

Vertical composition gradients of ternary alloy thin films find applications in numerous device structures. Up to now such gradients along the growth direction have not been realized by standard pulsed laser deposition (PLD) systems. In this study, we propose an approach based on a single elliptically segmented PLD target suited for the epitaxial growth of vertically graded layers. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00100
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http://dx.doi.org/10.1021/acscombsci.8b00100DOI Listing
November 2018
5 Reads

Identification of Novel Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors by Kinase Activity-Based High-Throughput Screening for Anticancer Therapeutics.

ACS Comb Sci 2018 Nov 23;20(11):660-671. Epub 2018 Oct 23.

Cancer Centre, Faculty of Health Sciences , University of Macau , Taipa , Macau , China.

Warburg effect, a preference of aerobic glycolysis for energy production even in the presence of adequate oxygen, is one of the most prominent distinctions of cancer cells from their normal equivalents. Upregulated pyruvate dehydrogenase kinase 1 (PDK1) was found to dominate the pivotal switch from mitochondrial respiration to aerobic glycolysis by inactivating pyruvate dehydrogenase (PDH) in cancer cells. PDK1 inhibition may lead to an unfavorable environment for cancer cells, which presents an opportunity for anticancer therapy. Read More

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http://pubs.acs.org/doi/10.1021/acscombsci.8b00104
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http://dx.doi.org/10.1021/acscombsci.8b00104DOI Listing
November 2018
8 Reads

Fluorescence Multiplexing with Spectral Imaging and Combinatorics.

ACS Comb Sci 2018 Nov 30;20(11):653-659. Epub 2018 Oct 30.

Department of Pharmacological Sciences , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.

Ultraviolet-to-infrared fluorescence is a versatile and accessible assay modality but is notoriously hard to multiplex due to overlap of wide emission spectra. We present an approach for fluorescence called multiplexing using spectral imaging and combinatorics (MuSIC). MuSIC consists of creating new independent probes from covalently linked combinations of individual fluorophores, leveraging the wide palette of currently available probes with the mathematical power of combinatorics. Read More

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http://dx.doi.org/10.1021/acscombsci.8b00101DOI Listing
November 2018
2 Reads