Search our Database of Scientific Publications and Authors

I’m looking for a

    683 results match your criteria ACS Combinatorial Science [Journal]

    1 OF 14

    High-Throughput Synthesis and Characterisation of Eu Doped SrBaSiO Thin Film Phosphors.
    ACS Comb Sci 2018 Jun 7. Epub 2018 Jun 7.
    High-Throughput techniques have been employed for the synthesis and characterisation of thin film phosphors of Eu doped BaxSr2-xSiO4. Direct synthesis from evaporation of the constituent elements under a flux of atomic oxygen on a sapphire substrate at 850 °C was used to directly produce thin film libraries (415 nm thickness) of the crystalline orthosilicate phase with the desired compositional variation (0.24 > x > 1. Read More

    Facile One-Pot Parallel Synthesis of 3-Amino-1,2,4-triazoles.
    ACS Comb Sci 2018 Jun 18. Epub 2018 Jun 18.
    Enamine, Ltd. , 78 Chervonotkatska Street , Kyiv , 02094 , Ukraine.
    A 1,2,4-triazole motif is present in numerous commercialized and investigational bioactive molecules. Despite its importance for medicinal chemistry, there is a lack of convenient combinatorial approaches toward this molecular core. Herein, we present a synthetic strategy suitable for the quick preparation of a library of structurally diverse 1,2,4-triazoles in a one-pot setting. Read More

    Photolabile Linkers for Solid-Phase Synthesis.
    ACS Comb Sci 2018 Jun 4. Epub 2018 Jun 4.
    Photolabile linkers are the subjects of intense research, because they allow the release of the target molecule simply by irradiation. Photochemical substrate release is often facilitated without additional reagents under mild reaction conditions, which may even be environmentally friendly and appealing in the context of greener chemistry. The mild conditions may, furthermore, become attractive for applications of released crude material in subsequent biological screening experiments, where contamination with cleavage reagents would be detrimental. Read More

    Molecular Docking Analysis and Biochemical Evaluation of Levansucrase from Sphingobium chungbukense DJ77.
    ACS Comb Sci 2018 Jun 15. Epub 2018 Jun 15.
    School of Biological Sciences , Chungbuk National University , 1 Chungdae-Ro , Seowon-Gu , Cheongju 28644 , Korea.
    Bacterial exopolymer Levan (β-(2,6) polyfructan) synthesized by levansucrase has attracted interest for various applications due to its low intrinsic viscosity compared with other polysaccharides. We report a novel levansucrase (Lsc) isolated from Sphingobium chunbukense DJ77 and verify its biochemical characteristics by comparative analysis of molecular docking analysis (MOE) and catalytic residue analysis. The complete sequence of the Lsc encoding gene ( lsc) was cloned under the direction of the T7 promoter and purified in an Escherichia coli BL21 (DE3) protein expression system. Read More

    CiPerGenesis, A Mutagenesis Approach that Produces Small Libraries of Circularly Permuted Proteins Randomly Opened at a Focused Region: Testing on the Green Fluorescent Protein.
    ACS Comb Sci 2018 Jun 12. Epub 2018 Jun 12.
    Instituto de Biotecnología , Universidad Nacional Autónoma de México , Avenida Universidad 2001 , Cuernavaca , Morelos 62210 , México.
    Circularly permuted proteins (cpPs) represent a novel type of mutant proteins with original termini that are covalently linked through a peptide connector and opened at any other place of the polypeptide backbone to create new ends. cpPs are finding wide applications in biotechnology because their properties may be quite different from those of the parental protein. However, the actual challenge for the creation of successful cpPs is to identify those peptide bonds that can be broken to create new termini and ensure functional and well-folded cpPs. Read More

    Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.
    ACS Comb Sci 2018 Jun 5. Epub 2018 Jun 5.
    University of Minnesota-Twin Cities , Department of Chemical Engineering and Materials Science , 421 Washington Avenue Southeast , Minneapolis , Minnesota 55455 , United States.
    Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. Read More

    Out-of-Plane Ionic Conductivity Measurement Configuration for High-Throughput Experiments.
    ACS Comb Sci 2018 Jun 12. Epub 2018 Jun 12.
    Materials Science and Engineering , Northwestern University , Evanston , Illinois 60208 , United States.
    An approach for measuring conductivity of thin-film electrolytes in an out-of-plane configuration, amenable to high-throughput experimentation, is presented. A comprehensive analysis of the geometric requirements for success is performed. Using samaria-doped ceria (CeSmO, SDC) excellent agreement between bulk samples and thin films with continuous and patterned electrodes, 100-500 μm in diameter, is demonstrated. Read More

    Combinatorial Nitrogen Gradients in Sputtered Thin Films.
    ACS Comb Sci 2018 Jun 7. Epub 2018 Jun 7.
    Materials Science Center , National Renewable Energy Laboratory , Golden , Colorado 80401 , United States.
    High-throughput synthesis and characterization methods can significantly accelerate the rate of experimental research. For physical vapor deposition (PVD), these methods include combinatorial sputtering with intentional gradients of metal/metalloid composition, temperature, and thickness across the substrate. However, many other synthesis parameters still remain out of reach for combinatorial methods. Read More

    Protein-Induced Fluorescence Enhancement Based Detection of Plasmodium falciparum Glutamate Dehydrogenase Using Carbon Dot Coupled Specific Aptamer.
    ACS Comb Sci 2018 Jun 10;20(6):350-357. Epub 2018 May 10.
    Department of Biosciences and Bioengineering , Indian Institute of Technology Guwahati , Guwahati , Assam 781039 , India.
    A novel 90-mer long ssDNA aptamer (NG3) covering a 40-mer random region targeting Plasmodium falciparum glutamate dehydrogenase ( PfGDH) developed through systematic evolution of ligands by exponential enrichment (SELEX) technique. The binding affinity of the aptamer to PfGDH discerned by circular dichroism (CD) was 0.5 ± 0. Read More

    Oxidative Modification of Tryptophan-Containing Peptides.
    ACS Comb Sci 2018 Jun 11;20(6):344-349. Epub 2018 May 11.
    Department of Chemistry , Technical University of Denmark , DK-2800 Kongens Lyngby , Denmark.
    We herein present a broadly useful method for the chemoselective modification of a wide range of tryptophan-containing peptides. Exposing a tryptophan-containing peptide to 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted in a selective cyclodehydration between the peptide backbone and the indole side chain of tryptophan to form a fully conjugated indolyl-oxazole moiety. The modified peptides show a characteristic and significant emission maximum at 425 nm, thus making the method a useful strategy for fluorescence labeling. Read More

    A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer.
    ACS Comb Sci 2018 Jun 7;20(6):330-334. Epub 2018 May 7.
    Department of Chemistry and Biochemistry , The University of Texas at Dallas , Richardson , Texas 75080 , United States.
    We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). Read More

    How Transparent Oxides Gain Some Color: Discovery of a CeNiO Reduced Bandgap Phase As an Absorber for Photovoltaics.
    ACS Comb Sci 2018 Jun 2;20(6):366-376. Epub 2018 May 2.
    Department of Chemistry, Center for Nanotechnology & Advanced Materials , Bar Ilan University , 5290002 Ramat Gan , Israel.
    In this work, we describe the formation of a reduced bandgap CeNiO phase, which, to our knowledge, has not been previously reported, and we show how it is utilized as an absorber layer in a photovoltaic cell. The CeNiO phase is prepared by a combinatorial materials science approach, where a library containing a continuous compositional spread of Ce NiO is formed by pulsed laser deposition (PLD); a method that has not been used in the past to form Ce-Ni-O materials. The library displays a reduced bandgap throughout, calculated to be 1. Read More

    Polycyclic Sulfoximines as New Scaffolds for Drug Discovery.
    ACS Comb Sci 2018 Jun 9;20(6):335-343. Epub 2018 May 9.
    Syncom B.V. , Kadijk 3 , 9747 AT Groningen , The Netherlands.
    The design and synthesis of three novel polycyclic scaffolds containing sulfoximines are presented in this work, which exemplify that sulfoximines represent a real opportunity for the discovery of new drug candidates. Additionally, the structures present at least two points of diversification and contain a high level of sp-character, hence being very interesting 3D scaffolds. The compounds synthesized were added to the compound collection of the European Lead Factory. Read More

    Current Parallel Solid-Phase Synthesis of Drug-like Oxadiazole and Thiadiazole Derivatives for Combinatorial Chemistry.
    ACS Comb Sci 2018 Jun 7;20(6):309-329. Epub 2018 May 7.
    Innovative Drug Library Research Center, Department of Chemistry, College of Science , Dongguk University , 26, 3-ga, Pil-dong , Jung-gu, Seoul 04620 , Korea.
    Solid-phase organic synthesis is a powerful tool in the synthesis of small organic molecules and building of libraries of compounds for drug discovery. Heterocyclic compounds are important components of the drug discovery field as well and serve as a core for hundreds of marketed drugs. In particular, oxadiazole and thiadiazole cores are compounds of great interest due to their comprehensive biological activities and structural features. Read More

    CsF-Catalyzed Transannulation Reaction of Oxazolones: Diastereoselective Synthesis of Diversified trans- N-(6-Oxo-1,4,5,6-tetrahydropyrimidin-5-yl)benzamides with Arylidene Azlactones and Amidines.
    ACS Comb Sci 2018 Jun 1;20(6):358-365. Epub 2018 May 1.
    Department of Chemistry , University of Isfahan , Isfahan 81746-73441 , Iran.
    A versatile and straightforward synthetic strategy for the construction of new tetrasubstituted 1,3-diazinones is described. The procedure is based on CsF-catalyzed, microwave-assisted, ring transformation reaction of arylidene azlactones with amidines. Moreover, this technique provides diversified trans- N-(6-oxo-1,4,5,6-tetrahydropyrimidin-5-yl)benzamides with a good antimicrobial activity. Read More

    Development and Synthesis of DNA-Encoded Benzimidazole Library.
    ACS Comb Sci 2018 May 25;20(5):251-255. Epub 2018 Apr 25.
    GlaxoSmithKline , Platform Technology & Science , 200 Cambridgepark Drive , Cambridge , Massachusetts 02140 , United States.
    Encoded library technology (ELT) is an effective approach to the discovery of novel small-molecule ligands for biological targets. A key factor for the success of the technology is the chemical diversity of the libraries. Here we report the development of DNA-conjugated benzimidazoles. Read More

    Acid-Promoted One-Pot Synthesis of Substituted Furan and 6-Methylpyrazin-2(1 H)-one Derivatives via Allene Intermediate Formed in Situ.
    ACS Comb Sci 2018 May 11;20(5):292-297. Epub 2018 Apr 11.
    Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI , Chongqing University of Arts and Sciences , 319 Honghe Avenue , Yongchuan, Chongqing , 402160 , China.
    Under the acidic conditions, substituted furans were constructed from γ-alkynyl ketones through corresponding allene intermediates in one-pot. The methodology was also tailored to a series of the Ugi reaction products for the synthesis of 6-methylpyrazin-2(1 H)-one derivatives. The current method offered significant advantages for the combinatorial applications of these chemical scaffolds. Read More

    A Parallel Approach to 7-(Hetero)arylpyrazolo[1,5- a]pyrimidin-5-ones.
    ACS Comb Sci 2018 May 6;20(5):256-260. Epub 2018 Apr 6.
    Pfizer Worldwide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
    A modular, two-pot assembly of 7-arylpyrazolo[1,5- a]pyrimidones from aryl/heteroaryl halides and aminopyrazoles in library format was developed. Sonogashira coupling of aryl bromides with triethyl orthopropiolate, followed by in situ orthoester hydrolysis, provides access to β-aryl ynoates, which undergo regioselective cyclocondensation with aminopyrazoles. The ability to vary the C7 vector of 7-arylpyrazolo[1,5- a]pyrimidones in two steps using readily available (hetero)aryl halides significantly enhances synthetic access to this challenging vector. Read More

    Automated High-Throughput Synthesis of Protein-Loaded Polyanhydride Nanoparticle Libraries.
    ACS Comb Sci 2018 May 10;20(5):298-307. Epub 2018 Apr 10.
    Department of Chemical and Biological Engineering and Nanovaccine Institute , Iowa State University , Ames , Iowa 50011 , United States.
    The development of high-throughput techniques and combinatorial libraries can facilitate rapid synthesis and screening of biomaterial-based nanocarriers for drug and vaccine delivery. This study describes a high-throughput method using an automated robot for synthesizing polyanhydride nanoparticles encapsulating proteins. Polyanhydrides are a class of safe and biodegradable polymers that have been widely used as drug and vaccine delivery vehicles. Read More

    Solid-Phase Synthesis of β-Hydroxy Ketones Via DNA-Compatible Organocatalytic Aldol Reactions.
    ACS Comb Sci 2018 May 3;20(5):277-281. Epub 2018 Apr 3.
    Department of Chemistry , The Scripps Research Institute , 130 Scripps Way , Jupiter , Florida 33458 , United States.
    One-bead one-compound (OBOC) libraries constructed by solid-phase split-and-pool synthesis are a valuable source of protein ligands. Most OBOC libraries are composed of oligoamides, particularly peptides, peptoids, and peptoid-inspired molecules. Further diversification of the chemical space covered by OBOC libraries is desirable. Read More

    Construction of Druglike 2-Amido Benzo[ d]imidazole Analogues via Desulfurative Cyclization of Thiourea Intermediate Resin on Solid-Phase.
    ACS Comb Sci 2018 May 26;20(5):282-291. Epub 2018 Mar 26.
    Innovative Drug Library Research Center, Department of Chemistry, College of Science , Dongguk University , 26, 3-ga, Pil-dong , Jung-gu , Seoul 100-715 , Korea.
    A 2-amido benzo[ d]imidazole library has been constructed by solid-phase synthesis. The key step of this solid-phase synthesis involves the preparation of polymer-bound 2-amino benzo[ d]imidazole resin through desulfurative cyclization of thiourea resin using 2-chloro-1,3-dimethylimidazolinium chloride and N, N-diisopropylethylamine in dichloromethane (DCM), and the resin is then functionalized by acylation at the 2-amine position to afford 2-amidobenzo[ d]imidazole resin. In the case of 2-amidobenzo[ d]imidazole resin having a p-I or m-NO, the resin was further functionalized by Suzuki/Sonogashira-coupling ( p-I) and reduction to the primary amine ( m-NO) followed by acylation. Read More

    Development and Application of a Sensitive Peptide Reporter to Discover 20S Proteasome Stimulators.
    ACS Comb Sci 2018 May 23;20(5):269-276. Epub 2018 Mar 23.
    Department of Medicinal Chemistry and Molecular Pharmacology , Purdue University , 575 West Stadium Avenue , West Lafayette , Indiana 47907 , United States.
    To attenuate an overabundance of cellular protein, it has been hypothesized that the 20S core particle (20S CP) of the proteasome can be chemically stimulated to degrade proteins into nontoxic peptides more quickly. Screening for small molecule 20S CP stimulators is typically performed with a reporter peptide composed of four amino acids and a coumarin group that is released upon proteasome-mediated hydrolysis to generate a fluorescent signal. Screening with this small reporter can lead to false negatives because the reporter peptide is rapidly turned-over without stimulation. Read More

    Aptamer-Based Paper Strip Sensor for Detecting Vibrio fischeri.
    ACS Comb Sci 2018 May 22;20(5):261-268. Epub 2018 Mar 22.
    School of Biological Sciences , Chungbuk National University 1 Chungdae-Ro , Seowon-Gu, Cheongju 28644 , South Korea.
    Aptamer-based paper strip sensor for detecting Vibrio fischeri was developed. Our method was based on the aptamer sandwich assay between whole live cells, V. fischeri and DNA aptamer probes. Read More

    A General Small-Angle X-ray Scattering-Based Screening Protocol Validated for Protein-RNA Interactions.
    ACS Comb Sci 2018 Apr 23;20(4):197-202. Epub 2018 Mar 23.
    Structural and Computational Biology Unit , EMBL Heidelberg , Meyerhofstrasse 1 , 69126 Heidelberg , Germany.
    We present a screening protocol utilizing small-angle X-ray scattering (SAXS) to obtain structural information on biomolecular interactions independent of prior knowledge, so as to complement affinity-based screening and provide leads for further exploration. This protocol categorizes ligand titrations by computing pairwise agreement between curves, and separately estimates affinities by quantifying complex formation as a departure from the linear sum properties of solution SAXS. The protocol is validated by sparse sequence search around the native poly uridine RNA motifs of the two-RRM domain Sex-lethal protein (Sxl). Read More

    Rapid Assessment of Sputtered Nanoparticle Ionic Liquid Combinations.
    ACS Comb Sci 2018 Apr 21;20(4):243-250. Epub 2018 Mar 21.
    Werkstoffe der Mikrotechnik, Institut für Werkstoffe, Fakultät für Maschinenbau , Ruhr-Universität Bochum , Universitätsstrasse 150 , D-44801 Bochum , Germany.
    A high-throughput method is presented for the efficient assessment of the formation and stability of nanoparticle suspensions in ionic liquids which differ in their cations and anions. As a proof of principle, Ag was sputtered on a cavity array filled with 9 different ionic liquids. Not all nanoparticle ionic liquid combinations form a stable suspension with separated nanoparticles. Read More

    Influences of W Content on the Phase Transformation Properties and the Associated Stress Change in Thin Film Substrate Combinations Studied by Fabrication and Characterization of Thin Film VW O Materials Libraries.
    ACS Comb Sci 2018 Apr 12;20(4):229-236. Epub 2018 Mar 12.
    Institute for Materials , Ruhr-Universität Bochum , D-44801 Bochum , Germany.
    The mechanical stress change of VO film substrate combinations during their reversible phase transformation makes them promising for applications in micro/nanoactuators. VW O thin film libraries were fabricated by reactive combinatorial cosputtering to investigate the effects of the addition of W on mechanical and other transformation properties. High-throughput characterization methods were used to systematically determine the composition spread, crystalline structure, surface topography, as well as the temperature-dependent phase transformation properties, that is, the hysteresis curves of the resistance and stress change. Read More

    A Bioactive Trypanosoma cruzi Bromodomain Inhibitor from Chemically Engineered Extracts.
    ACS Comb Sci 2018 Apr 2;20(4):220-228. Epub 2018 Mar 2.
    Facultad de Ciencias Bioquímicas y Farmacéuticas , Universidad Nacional de Rosario , Suipacha 531 , CP2000 , Rosario , Argentina.
    A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that interacts with TcBDF3 with affinity in the submicromolar range and that shows interesting antiparasitic properties against the different life cycle stages of T. cruzi. Read More

    Comparison of Cell Permeability of Cyclic Peptoids and Linear Peptoids.
    ACS Comb Sci 2018 Apr 1;20(4):237-242. Epub 2018 Mar 1.
    Department of Chemistry and Division of Advanced Material Science , Pohang University of Science and Technology (POSTECH) , Pohang 37673 , South Korea.
    Cyclic peptoids are emerging as an attractive class of peptidomimetics. Compared to their linear counterparts, cyclic peptoids should have increased conformational rigidity and preorganized structures, enabling them to bind more tightly to target proteins without major entropy penalty. Because cyclic peptoids lack the amide protons in their backbones like linear peptoids, it is perceived that cyclic peptoids are seemingly cell permeable as much as linear peptoids. Read More

    Synthesis of Highly Substituted Imidazole Uracil Containing Molecules via Ugi-4CR and Passerini-3CR.
    ACS Comb Sci 2018 Apr 26;20(4):192-196. Epub 2018 Feb 26.
    University of Groningen , Department of Drug Design , A. Deusinglaan 1 , 9713 AV Groningen , The Netherlands.
    The synthesis of uracil/thymine containing tetra/trisubstituted imidazole derivatives was demonstrated using Ugi/Passerini-reaction followed by a postcyclization reaction sequence. The approach enables the one-pot facile construction of diverse compounds in moderate to excellent yields (47-82%). The 5-fluorouracil and 5-methyluracil moieties afford potentially bioactive molecules with drug-like properties. Read More

    Synthesis of Cyclic Peptides as Potential Anti-Malarials.
    ACS Comb Sci 2018 Apr 26;20(4):212-219. Epub 2018 Feb 26.
    Cátedra de Química Farmacéutica, (DQO), Facultad de Química , Universidad de la República , Gral. Flores 2124 , CP 11800 , Montevideo , Uruguay.
    The results from the synthesis of peptides by Fmoc/SPPS on a 2-CTC resin and then lactamization in solution or solid phase for the preparation of cyclopeptides are presented. Both procedures allow the synthesis of the desired compounds in good to very good yield and with high cyclization efficiency for on-resin macrocyclization. In addition, the activities of the corresponding cyclopeptides against the chloroquine-resistant K1 strain of Plasmodium falciparum were evaluated. Read More

    Solid-Phase Synthesis of Pyrrole Derivatives through a Multicomponent Reaction Involving Lys-Containing Peptides.
    ACS Comb Sci 2018 Apr 22;20(4):187-191. Epub 2018 Feb 22.
    Catalysis and Peptide Research Unit , School of Health Sciences, University of KwaZulu-Natal , University Road , Westville, Durban 4001 , South Africa.
    The synthesis of pyrroles has received considerable attention because of their biological and pharmaceutical activities. Herein we describe a solid-phase multicomponent reaction that utilizes Lys as a N donor, β-nitrostyrenes, 1,3-dicarbonyl compounds, and FeCl as an easily accessible catalyst under microwave irradiation to afford the subsequent pyrrole derivatives in high conversions. The strategy combines three of the most powerful tools in modern synthetic chemistry: the solid-phase mode, microwave activation, and a multicomponent reaction. Read More

    Solid-Phase Synthesis and Antibacterial Activity of Cyclohexapeptide Wollamide B Analogs.
    ACS Comb Sci 2018 03 20;20(3):172-185. Epub 2018 Feb 20.
    Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy , University of Hawai'i at Hilo , 34 Rainbow Drive , Hilo , Hawaii 96720 , United States.
    Herein we report the antibacterial structure-activity relationships of cyclic hexapeptide wollamide analogs derived from solid-phase library synthesis. Wollamide B, a cyclic hexapeptide natural product, has been previously found to have activity against Mycobacterium bovis. To further evaluate its antimycobacterial/antibacterial potential, 27 peptides including wollamides A/B, and desotamide B, were synthesized and subsequently tested against a panel of clinically significant bacterial pathogens. Read More

    Regioselective Synthesis of Pyranone-Fused Indazoles via Reductive Cyclization and Alkyne Insertion.
    ACS Comb Sci 2018 03 13;20(3):156-163. Epub 2018 Feb 13.
    Department of Applied Chemistry , National Chiao-Tung University , 1001, Ta-Hseuh Road , Hsinchu 300-10 , Taiwan.
    A novel and efficient method for the one-pot synthesis of 2 H-indazole from readily available building blocks is reported. The reaction of 2-nitrobenzylamines with zinc and ammonium formate underwent partial reduction to nitroso-benzylamine followed by an intramolecular cyclization to afford 2 H-indazole via N-N bond formation. The carboxylic acid moiety of indazole was proceeded to regioselective alkyne insertion under ruthenium catalysis to form pyranone-fused indazoles. Read More

    Rapid Construction of Fe-Co-Ni Composition-Phase Map by Combinatorial Materials Chip Approach.
    ACS Comb Sci 2018 03 6;20(3):127-131. Epub 2018 Feb 6.
    Materials Genome Initiative Center , Shanghai Jiao Tong University , Shanghai 200240 , China.
    One hundred nanometer thick Fe-Co-Ni material chips were prepared and isothermally annealed at 500, 600, and 700 °C, respectively. Pixel-by-pixel composition and structural mapping was performed by microbeam X-ray at synchrotron light source. Diffraction images were recorded at a rate of 1 pattern/s. Read More

    Efficient Access to Imidazo[1,2- a]pyridines/pyrazines/pyrimidines via Catalyst-Free Annulation Reaction under Microwave Irradiation in Green Solvent.
    ACS Comb Sci 2018 03 7;20(3):164-171. Epub 2018 Feb 7.
    Department of Chemistry, School of Advanced Sciences , VIT University , Vellore - 632014 , India.
    An expeditious catalyst-free heteroannulation reaction for imidazo[1,2- a]pyridines/pyrimidines/pyrazines was developed in green solvent under microwave irradiation. Using HO-IPA as the reaction medium, various substituted 2-aminopyridines/pyrazines/pyrimidines underwent annulation reaction with α-bromoketones under microwave irradiation to provide the corresponding imidazo[1,2- a]pyridines/pyrimidines/pyrazines in excellent yields. The synthetic methodology appears to be very simple and superior to the already reported procedures with the high abundance of commercial reagents and great ability in expanding the molecular diversity. Read More

    Sortase-Mediated High-Throughput Screening Platform for Directed Enzyme Evolution.
    ACS Comb Sci 2018 Apr 2;20(4):203-211. Epub 2018 Feb 2.
    DWI-Leibniz-Institute for Interactive Materials , Forckenbeckstraße 50 , 52074 Aachen , Germany.
    Sortase-catalyzed ligations have emerged as powerful tools for the site-specific ligation of peptides and proteins in material science and biocatalysis. In this work, a directed sortase evolution strategy (SortEvolve) has been developed as a general high-throughput screening (HTS) platform to improve activity of sortase A (application 1) and to perform directed laccase evolution through a semipurification process in 96-well microtiter plate (MTP) (application 2). A semipurification process in polypropylene MTP (PP-MTP) is achieved through the anchor peptide LCI, which acts as adhesion promoter. Read More

    Detection of Circulating Tumor Cells Using Microfluidics.
    ACS Comb Sci 2018 03 2;20(3):107-126. Epub 2018 Feb 2.
    University of Agronomic Sciences and Veterinary Medicine, Bucharest , Romania , 050097.
    Metastasis is the main cause of death in cancer patients worldwide. During metastasis, cancer cells detach from the primary tumor and invade distant tissue. The cells that undergo this process are called circulating tumor cells (CTCs). Read More

    Crystallographic Structure Analysis of a Ti-Ta Thin Film Materials Library Fabricated by Combinatorial Magnetron Sputtering.
    ACS Comb Sci 2018 03 15;20(3):137-150. Epub 2018 Feb 15.
    Applied Crystallography and Materials Science, Department of Earth and Environmental Sciences, Faculty of Geosciences , Ludwig-Maximilians-Universität , 80333 München , Germany.
    Ti-Ta thin films exhibit properties that are of interest for applications as microactuators and as biomedical implants. A Ti-Ta thin film materials library was deposited at T = 25 °C by magnetron sputtering employing the combinatorial approach, which led to a compositional range of TiTa to TiTa. Subsequent high-throughput characterization methods permitted a quick and comprehensive study of the crystallographic, microstructural, and morphological properties, which strongly depend on the chemical composition. Read More

    Solid-Phase Synthesis of Oligopeptides Containing Sterically Hindered Amino Acids on Nonswellable Resin Using 3-Nitro-1,2,4-triazol-1-yl-tris(pyrrolidin-1-yl)phosphonium Hexafluorophosphate (PyNTP) as the Condensing Reagent.
    ACS Comb Sci 2018 03 30;20(3):132-136. Epub 2018 Jan 30.
    Faculty of Pharmaceutical Sciences , Tokyo University of Science , 2641 Yamazaki , Noda , Chiba 278-8510 , Japan.
    Peptides are still difficult to synthesize when they contain sterically hindered amino acids, such as α,α-disubstituted amino acids and N-substituted amino acids. In this study, solid-phase syntheses of oligopeptides containing multiple α-aminoisobutyric acid (Aib) residues were performed in high yields by using a nonswellable resin as the solid-support and 3-nitro-1,2,4-triazol-1-yl-tris(pyrrolidin-1-yl)phosphonium hexafluorophosphate (PyNTP) as the condensing reagent. Read More

    Enediyne-Comprising Amino Aldehydes in the Passerini Reaction.
    ACS Comb Sci 2018 03 30;20(3):151-155. Epub 2018 Jan 30.
    Division of Organic Chemistry and Biochemistry , Ruđer Bošković Institute , Bijenička cesta 54 , 10000 Zagreb , Croatia.
    Multicomponent reactions represent a highly efficient approach to a broad spectrum of structurally diverse compounds starting from simple and affordable compounds. A focused library of tweezers-like compounds is prepared by employing the multicomponent Passerini reaction comprising enediyne-derived amino aldehydes. The reaction proceeds under mild conditions yielding Passerini products in good to excellent yields. Read More

    Sequential Multicomponent Strategy for the Diastereoselective Synthesis of Densely Functionalized Spirooxindole-Fused Thiazolidines.
    ACS Comb Sci 2018 02 25;20(2):98-105. Epub 2018 Jan 25.
    Dipartimento di Chimica, Università degli Studi di Milano , via Golgi 19, Milano, 20133, Italy.
    We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures affording the products in typically good yields. The obtained thiazolidines proved to be suitable substrates for further transformations. Read More

    Solid-Phase Synthesis of β-Amino Ketones Via DNA-Compatible Organocatalytic Mannich Reactions.
    ACS Comb Sci 2018 02 24;20(2):55-60. Epub 2018 Jan 24.
    Department of Chemistry The Scripps Research Institute 130 Scripps Way, Jupiter, Florida 33458, United States.
    One-bead-one-compound (OBOC) libraries constructed by solid-phase split-and-pool synthesis are a valuable source of protein ligands. Most OBOC libraries are comprised of oligoamides, particularly peptides, peptoids, and peptoid-inspired molecules. Further diversification of the chemical space covered by OBOC libraries is desirable. Read More

    Construction of 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Library with a High Level of Skeletal Diversity Based on Branching Diversity-Oriented Synthesis on Solid-Phase Supports.
    ACS Comb Sci 2018 02 24;20(2):82-97. Epub 2018 Jan 24.
    Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
    An efficient solid-phase synthetic route for the construction of 1,3,4-oxadiazole and 1,3,4-thiadiazole libraries based on branching diversity-oriented synthesis (DOS) has been developed in this study. The core skeleton resins, 1,3,4-oxadiazole and 1,3,4-thiadiazole, were obtained through desulfurative and dehydrative cyclizations of thiosemicarbazide resin, respectively. Various functional groups have been introduced to the core skeleton resins, such as aryl, amine, amide, urea, thiourea, and an amino acid. Read More

    DNA-Compatible Solid-Phase Combinatorial Synthesis of β-Cyanoacrylamides and Related Electrophiles.
    ACS Comb Sci 2018 02 17;20(2):61-69. Epub 2018 Jan 17.
    Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.
    We demonstrate that the Knoevenagel condensation can be exploited in combinatorial synthesis on the solid phase. Condensation products from such reactions were structurally characterized, and their Michael reactivity with thiol and phosphine nucleophiles is described. Cyanoacrylamides were previously reported to react reversibly with thiols, and notably, we show that dilution into low pH buffer can trap covalent adducts, which are isolable via chromatography. Read More

    Discrete Fourier Transform-Based Multivariate Image Analysis: Application to Modeling of Aromatase Inhibitory Activity.
    ACS Comb Sci 2018 02 22;20(2):75-81. Epub 2018 Jan 22.
    Unidad de Toxicología Experimental, Universidad de Ciencias Médicas "Serafín Ruiz de Zárate Ruiz" , Santa Clara, 50200 Villa Clara, Cuba.
    We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally diverse chemical compound data sets. Here we report the first practical application of this method in the screening of molecular entities of therapeutic interest, with human aromatase inhibitory activity as the case study. We developed an ensemble classification model based on the two-dimensional (2D) DFT MIA-QSAR descriptors, with which we screened the NCI Diversity Set V (1593 compounds) and obtained 34 chemical compounds with possible aromatase inhibitory activity. Read More

    Application of the Open qPCR Instrument for the in Vitro Selection of DNA Aptamers against Epidermal Growth Factor Receptor and Drosophila C Virus.
    ACS Comb Sci 2018 02 17;20(2):45-54. Epub 2018 Jan 17.
    University of Idaho , Department of Chemistry, 875 Perimeter Drive, Moscow, Idaho 83844-2343, United States.
    The low-cost Open qPCR instrument can be used for different tasks in the aptamer selection process: quantification of DNA, cycle course optimization, screening, and final binding characterization. We have selected aptamers against whole Drosophila C virus (DCV) particles and recombinant epidermal growth factor receptor (EGFR). We performed systematic evolution of ligands by exponential enrichment (SELEX) using the Open qPCR to optimize each amplification step. Read More

    Application of High-Throughput Seebeck Microprobe Measurements on Thermoelectric Half-Heusler Thin Film Combinatorial Material Libraries.
    ACS Comb Sci 2018 01 21;20(1):1-18. Epub 2017 Dec 21.
    Institute of Materials Research, German Aerospace Center , D-51170 Cologne, Germany.
    In view of the variety and complexity of thermoelectric (TE) material systems, combinatorial approaches to materials development come to the fore for identifying new promising compounds. The success of this approach is related to the availability and reliability of high-throughput characterization methods for identifying interrelations between materials structures and properties within the composition spread libraries. A meaningful characterization starts with determination of the Seebeck coefficient as a major feature of TE materials. Read More

    An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries.
    ACS Comb Sci 2018 01 27;20(1):35-43. Epub 2017 Dec 27.
    Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.
    An approach to the parallel synthesis of hydantoin libraries by reaction of in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility of the method, a library of 1158 hydantoins designed according to the lead-likeness criteria (MW 200-350, cLogP 1-3) was prepared. The success rate of the method was analyzed as a function of physicochemical parameters of the products, and it was found that the method can be considered as a tool for lead-oriented synthesis. Read More

    Novel Multicomponent Synthesis of Pyridine-Pyrimidines and Their Bis-Derivatives Catalyzed by Triazine Diphosphonium Hydrogen Sulfate Ionic Liquid Supported on Functionalized Nanosilica.
    ACS Comb Sci 2018 01 27;20(1):19-25. Epub 2017 Dec 27.
    Catalysis Division, Department of Chemistry, University of Isfahan , Isfahan 81746-73441, Iran.
    In this Research Article, we report an efficient synthesis of 1,3-dimethyl-5-aryl-7-(pyridine-3(2)(4)-yl)pyrimidine-2,4(1H,3H)-diones via a three-component reaction of aryl aldehydes, 1,3-dimethyl-6-aminouracil and carbonitriles in the presences of triazine diphosphonium hydrogen sulfate ionic liquid supported on functionalized nanosilica (APTADPHS-nSiO) as a reusable catalyst under microwave irradiation and solvent-free conditions. The bis-derivatives of pyridine-pyrimidines were also efficiently prepared from dialdehydes and dinitriles. In addition, 3-methyl-1H-pyrazole-5-amine was used successfully instead of 1,3-dimethyl-6-aminouracil under the same conditions to afford the corresponding products in high yields. Read More

    Library-to-Library Synthesis of Highly Substituted α-Aminomethyl Tetrazoles via Ugi Reaction.
    ACS Comb Sci 2018 02 4;20(2):70-74. Epub 2018 Jan 4.
    University of Groningen , Department of Drug Design, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
    α-Aminomethyl tetrazoles, recently made accessible by an Ugi multicomponent reaction (MCR), were shown to be excellent starting materials for a further Ugi MCR, yielding substituted N-methyl-2-(((1-methyl-1H-tetrazol-5-yl)methyl)amino)acetamides having four points of diversity in a library-to-library approach. The scope and limitations of the two-step sequence was explored by conducting more than 50 reactions. Irrespective of electron-rich and electron-deficient oxo-components and the nature of the isocyanide component, the reactions give excellent yields. Read More

    1 OF 14