387501517 - EP 0983983 A3 2000-07-05 - Combinatorial synthesis and analysis of organometallic compounds and catalysts - [origin: EP0978499A2] Methodologies for the synthesis, screening and characterisation of organometallic compounds and catalysts (eg homogenous catalysts), including combinatorial synthesis, screening and characterisation of libraries of supported and unsupported organometallic compounds and catalysts (eg homogenous catalysts). The methods can be applied to the preparation and screening of large numbers of organometallic compounds which can be used not only as catalysts (eg homogeneous catalysts), but also as additives and therapeutic agents.[origin: EP0978499A2] Methodologies for the synthesis, screening and characterisation of organometallic compounds and catalysts (eg homogenous catalysts), including combinatorial synthesis, screening and characterisation of libraries of supported and unsupported organometallic compounds and catalysts (eg homogenous catalysts). The methods can be
Dynamic combinatorial chemistry utilises reversible reactions to set up a dynamic library of molecules, with the library composition determined by the thermodynamic stability of each library member. Upon addition of a protein template, any library members which bind to the template are stabilised and amplified. Analysis of the library composition enables the identification of molecules which bind to the template protein. The suitability of two enzyme catalysed reactions catalysed by N-acetylneuraminic acid aldolase and subtilisin® Carlsberg was investigated for use in the synthesis of a DCL. A 173 component dynamic combinatorial library was successfully synthesised using these reactions with the resulting library screened against two protein template molecules, wheat germ agglutinin and Div1B. Several methods were investigated for the simplification of DCL analysis including the immobilisation of protein template molecules and the segregation of DCL proteins using semi-permiable membranes, ...
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Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research.
Since oxidative cellular damage contributes to the development of cancers, heart disease and ageing, the synthesis of antioxidative agents which are able to either prevent or mitigate oxidative stress to cells is an important area of investigation. Combinatorial chemistry has had a profound impact on the discovery and optimisation of potential lead compounds, especially in the medicinal field. This review details recent examples of combinatorial chemistry dealing with the synthesis of novel antioxidants with an emphasis on solid phase compound synthesis and parallel library synthesis.. Full text not available from this repository.. ...
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews dealing with various topic...
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The goal of this thesis was to develop a method for efficiently synthesizing a large suite of asymmetric oligoester ion channel-forming compounds. A solid-phase organic synthesis (SPOS) approach on Wang resin was used to generate the ion channel candidates. A follow-on goal is to survey the compounds produced to uncover structure-related controls on ion transport activity. Two classes of building blocks were used to generate the oligoesters - head groups and cores. The core building blocks were three omega-hydroxy acid derivatives six, eight and twelve carbons in length and the alcohol protected as a tetrahydropyranyl ether. The head group building blocks were either a glutaric acid monoester derivative of varying lipophilicity (12 to 16 carbon long alkyl tail) or a beta-hydroxy acid derivative; these building blocks used a tert-butyldimethylsilyl ether for alcohol protection. Optimized conditions for building block coupling, deprotection, and product cleavage were first established by the ...
Establishing synthesis methods for a target material constitutes a grand challenge in materials research, which is compounded with use-inspired specifications on the format of the material. Solar photochemistry using thin film materials is a promising technology for which many complex materials are being proposed, and the present work describes application of combinatorial methods to explore the synthesis of predicted La-Bi-Cu oxysulfide photocathodes, in particular alloys of LaCuOS and BiCuOS. The variation in concentration of three cations and two anions in thin film materials, and crystallization thereof, is achieved by a combination of reactive sputtering and thermal processes including reactive annealing and rapid thermal processing. Composition and structural characterization establish composition-processing-structure relationships that highlight the breadth of processing conditions required for synthesis of LaCuOS and BiCuOS. The relative irreducibility of La oxides and limited diffusion ...
TentaGel® Macrobeads are highlighted by extraordinary large particle diameters and high capacities based on the TentaGel® technology and designed for single bead synthesis and single bead analysis ...
Multicomponent reactions are flexible reactions for the rapid generation of complex molecules with often biologically relevant scaffold structures. Combined with the ease of parallelization and the exploratory power with regard to chemical space, multicomponent reactions have attracted significant attention
Enzyme inhibition forms the basis of much of the medicinal chemistry used in the treatment of disease. β-Sultams are cyclic sulfonamides which are both β-lactam analogues and potential pro drugs of taurine and substituted taurines: as their hydrolysis products. Two β-sultams, their hydrolysis products and a range of dicarboxylic acids were tested as inhibitors of BcII, a metallo-β-lactamase enzyme. The two β-sultams, their hydrolysis products and some related compounds were also tested as inhibitors of glutamine synthetase following work showing that β-sultam has an effect on neurotransmission in the CNS.. A novel β-sultam, 1,2-thiazetidine-3-carboxylate 1,1-dioxide (3-carboxy-β-sultam), has been synthesised via a four-step process from L cystine including the removal of a benzyl ester group from benzyl 3-carboxylate-β-sultam utilising sodium in liquid ammonia. The product has been characterised by NMR and MS.. The rate of hydrolysis of 3-carboxy-β-sultam was investigated using 1H NMR ...
Title:Tandem Multicomponent Reactions Toward the Design and Synthesis of Novel Antibacterial and Cytotoxic Motifs. VOLUME: 20 ISSUE: 11. Author(s):Mohammad H. Semreen, Raafat El-Awady, Raed Abu-Odeh, Maha Saber-Ayad, Raed A. Al-Qawasmeh, Salem Chouaib, Wolfgang Voelter and Taleb H. Al-Tel. Affiliation:Sharjah Institute for Medical Research, University of Sharjah, P.O.Box 27272, Sharjah, UAE.. Keywords:Imidazopyridines, Ugi reaction, multicomponent reaction, Groebke-Blackburn reaction, antibacterial, hospital resistant strains, anticancer.. Abstract:The synthesis of polysubstituted imidazopyridines and imidazopyrazines through the orthogonal union of Groebke-Blackburn and Ugi reactions is described. These motifs were produced efficiently in a tandem operation without intermediate isolation. The synthesized scaffolds were biologically evaluated and found to posses potent anticancer and antibacterial activities. Importantly, some of these motifs (e.g. compound 5) were found to possess specific ...
International Scholarly Research Notices is a peer-reviewed, Open Access journal covering a wide range of subjects in science, technology, and medicine. The journals Editorial Board as well as its Table of Contents are divided into 108 subject areas that are covered within the journals scope.
The designing, synthesizing and screening of one-bead-one-compound (OBOC) combinatorial chemistry libraries against a single target ligand has been well developed. Recently, novel cholesterol/peptide hybrid combinatorial One-Bead-One-Compound (OBOC) combinatorial libraries have been developed and synthesized with self folding capabilities. The library design strategy was based on a similar pentamer and hexamer self-folding branched tricylic libraries previously developed. The cholic acid on the side chain of the carboxyl lysine is believed to interact with fixed hydrophobic amino acids at the amino-termini (position 5) of the twin branched L-amino acid arms and self-fold into a tricyclic molecule. The newly synthesized library has arginine (R) and Lysine (K) down-proportioned to 10 % for each position to decrease the probability of positive charge nonspecific binding. Thirty L-, D-, and unnatural amino acids were used in each position as building blocks. Hydrophobicity was fixed at position 5 ...
An apparatus for high-throughput combinatorial syntheses of organic molecules including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. A method of combinatorial synthesis of organic molecules is also disclosed.
Systems and methods for providing in situ, controllably variable concentrations of one, two or more chemical components on a substrate to produce an integrated materials chip. The component concentrations can vary linearly, quadratically or according to any other reasonable power law with one or two location coordinates. In one embodiment, a source and a mask with fixed or varying aperture widths and fixed or varying aperture spacings are used to produce the desired concentration envelope. In another embodiment, a mask with one or more movable apertures or openings provides a chemical component flux that varies with location on the substrate, in one or two dimensions. In another embodiment, flow of the chemical components through nuzzle slits provides the desired concentrations. An ion beam source, a sputtering source, a laser ablation source, a molecular beam source, a chemical vapor deposition source and/or an evaporative source can provide the chemical component(s) to be deposited on the substrate.
Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease.: A phenotypic high-throughput screen using ∼100,000 compounds prepared usin
N-Acylsulfonamides usually react with nucleophiles by acyl transfer and C-N bond fission. However, the hydrolysis of N-acyl -sultams is a sulfonyl transfer reaction that occurs with S-N fission and opening of the four-membered ring. Similar to other -sultams, the N-acyl derivatives are at least 106-fold more reactive than N-acyl sulfonamides. 3-Oxo--sultams are both -lactams and -sultams but also hydrolyze with preferential S-N bond fission.. ...
TentaGel® resins are grafted copolymers consisting of a low crosslinked polystyrene matrix on which polyethylene glycol (PEG or POE) is grafted. The PEG spacer is attached to the matrix via an ethyl ether group which increases stability towards acid treatment and minimizes PEG-leaching. As PEG is a chameleon type polymer with hydrophobic and hydrophilic properties, the graft copolymer shows modified physico chemical properties which are highly dominated by the PEG moiety (and no longer by the polystyrene matrix). These graft copolymers are pressure stable and can be used in batch processes as well as under continuous flow conditions. The PEG spacer is in the range of MW 3000 Da. This resin is synthesized from TentaGel® amine and the base labile 4-(hydroxymethyl)benzoic acid linker. It is a versatile support for the immobilization of carboxylic acids. The resulting ester bond is stable to strong acids but is cleaved by nucleophiles like amines, hydrazine or alkoxides. ...
Isogenica, Cambridge UK and Imperial College London secure funding from UKs Technology Strategy Board to develop gene library synthesis for synthetic
A novel bacteriophage lambda vector system was used to express in Escherichia coli a combinatorial library of Fab fragments of the mouse antibody repertoire. The system allows rapid and easy identification of monoclonal Fab fragments in a form suitable for genetic manipulation. It was possible to generate, in 2 weeks, large numbers of monoclonal Fab fragments against a transition state analog hapten. The methods described may supersede present-day hybridoma technology and facilitate the production of catalytic and other antibodies.. ...
FIG: 3 ORGANIC SYNTHESIS USING SOLID SUPPORT. 1) A cross linked, insoluble polymeric material that is inert to the condition of synthesis;. 2) Some means of linking the substrate to this solid phase that permits selective cleavage of some or all of the product from the solid support during synthesis for analysis of the extent of reaction(s), and ultimately to give the final product of interest;. 3) A chemical protection strategy to allow selective protection and deprotection of reactive groups.. Merrifield developed a series of chemical reactions that can be used to synthesise proteins. The direction of synthesis is opposite to that used in the cell. The intended carboxy terminal amino acid is anchored to a solid support. Then, the next amino acid is coupled to the first one. In order to prevent further chain growth at this point, the amino acid, which is added, has its amino group blocked. After the coupling step, the block is removed from the primary amino group and the coupling reaction is ...
AIM AND OBJECTIVE: The importance of acridine core structure and other heterocycles containing its framework is well known, as they are found in numerous compounds with a variety of biological effects. Pyridine is also an important solvent and heterocyclic nucleus for the design and synthesis of novel molecules with biological properties. It occurs in several natural compounds which are used as a precursor in agrochemicals and pharmaceuticals. The utility of nanostructured metal salts because of their small size and high surface area as catalysts in organic synthesis has drawn special attention due to their better properties such as slower reaction rate, reusability of the catalyst, and higher yields of products compared to the bulk size ...
Bentham Science Publishers would like to invite you to submit your research paper for publishing in the Journal of Combinatorial Chemistr ...
PharmaSeq, Inc., is a private company located near Princeton, NJ. Its business is in developing an ultra-small microtransponder tagging platform that has broad applications for the tagging and tracking of objects used in the consumer goods, industrial goods, life sciences and eventually clinical diagnostics industries.
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A versatile copper(i)-catalyzed cascade multicomponent reaction strategy between readily available (Z)-3-iodoacrylic acids, terminal alkynes, and primary amines is reported, leading to a great diversity of complex heterocyclic backbones based on biorelevant indole/lactam scaffolds.
The use of cyclic peptides in one-bead-one-compound libraries is limited by difficulties in sequencing hit compounds. Lacking a free N-terminal amine, such peptides cannot be sequenced by the Edman degradation approach, and complex fragmentation patterns are obtained by tandem mass spectrometry. To overcome this problem, we designed an alternative approach introducing a methionine residue within the macrocycle and as a linker to allow simultaneous ring-opening and release from the resin upon treatment with cyanogen bromide. The methionine linker was inverted relative to the peptide chain to allow the synthesis of cyclic peptides anchored by a lysine side chain and to avoid the presence of two C-terminal homoserine lactones on the released linear peptides. After MALDI-TOF MS/MS analysis, the peptides released from a single bead were sequenced manually and with a de novo sequencing software. The strategy described herein is compatible with commonly used amino acids and allows sequencing of cyclic ...
Dynamic covalent chemistry (DCvC) is a synthetic strategy employed by chemists to make complex supramolecular assemblies from discrete molecular building blocks. DCvC has allowed access to complex assemblies such as covalent organic frameworks, molecular knots, polymers, and novel macrocycles. Not to be confused with dynamic combinatorial chemistry, DCvC concerns only covalent bonding interactions. As such, it only encompasses a subset of supramolecular chemistries. The underlying idea is that rapid equilibration allows the coexistence of a variety of different species among which molecules can be selected with desired chemical, pharmaceutical and biological properties. For instance, the addition of a proper template will shift the equilibrium toward the component that forms the complex of higher stability (thermodynamic template effect). After the new equilibrium is established, the reaction conditions are modified to stop equilibration. The optimal binder for the template is then extracted ...
The Chemical Biology Thematic Group is engaged in a diverse range of research topics which span structural biology, enzymology, nucleic acid research, signalling pathways, single molecule biophysics, and biophysical chemistry of living tissues. Among the themes which unite the research being performed in this group is trying to learn new chemistry and physics from biological systems. We have projects relating to pharmaceutically relevant enzymes such as those involved in drug metabolism and antibiotic resistance; development of therapeutic agents in the control of inflammation, cancer and viral infections; the chemical biology of NO; quantification of bioenergetic markers of metabolism; self-assembly mechanisms of the HIV-1 virion capsid; liposome microarray systems to address membrane protein dynamics and recognition; studies on reactive oxygen species translocation across the aqueous/lipid membrane interface; RNAi/antisense technologies; dynamic combinatorial chemistry; protein dynamics and ...
Related Articles. Structure-Based Design of Inhibitors of the Aspartic Protease Endothiapepsin by Exploiting Dynamic Combinatorial Chemistry.. Angew Chem Int Ed Engl. 2014 Feb 14 ...
The blood-brain barrier (BBB) is a biological barrier that protects the brain from neurotoxic agents and regulates the influx and efflux of molecules required for its correct function. This stringent regulation hampers the passage of brain parenchyma-targeting drugs across the BBB. BBB shuttles have been proposed as a way to overcome this hurdle because these peptides can not only cross the BBB but also carry molecules which would otherwise be unable to cross the barrier unaided. Here we developed a new high-throughput screening methodology to identify new peptide BBB shuttles in a broadly unexplored chemical space. By introducing d-amino acids, this approach screens only protease-resistant peptides. This methodology combines combinatorial chemistry for peptide library synthesis, in vitro models mimicking the BBB for library evaluation and state-of-the-art mass spectrometry techniques to identify those peptides able to cross the in vitro assays. BBB shuttle synthesis was performed by the ...
TY - JOUR. T1 - Inactivation of Bacterial DD-Peptidase by β-Sultams. AU - Llinás, Antonio. AU - Ahmed, Naveed. AU - Cordaro, Massimiliano. AU - Laws, Andrew P.. AU - Frère, Jean Marie. AU - Delmarcelle, Michael. AU - Silvaggi, Nicholas R.. AU - Kelly, Judith A.. AU - Page, Michael I.. PY - 2005/5/31. Y1 - 2005/5/31. N2 - N-Acyl-β-sultams are time-dependent, irreversible active site-directed inhibitors of Streptomyces R61 DD-peptidase. The rate of inactivation is first order with respect to β-sultam concentration, and the second-order rate constants show a dependence on pH similar to that for the hydrolysis of a substrate. Inactivation is due to the formation of a stable 1:1 enzyme-inhibitor complex as a result of the active site serine being sulfonylated by the β-sultam as shown by ESI-MS analysis and by X-ray crystallography. A striking feature of the sulfonyl enzyme is that the inhibitor is not bound to the oxyanion hole but interacts extensively with the roof of the active site where ...