abstract：:Amino acids were immobilised by attaching them via a carbamate linker to Wang resin. These intermediates were converted to 1-(1,3-benzoxazol-2-yl)alkanamines over three steps, followed by coupling with 4-alkyl-6-chloro-1,3,5-triazine-2-amines to furnish the desired N-[1-(1,3-benzoxazol-2-yl)alkyl]-6-alkyl-1,3,5-triazi...

journal_title：Combinatorial chemistry & high throughput screening

authors： Dietrich H,Giencke W,Klein R

更新日期：2005-11-01 00:00:00

abstract：:As HTS technologies come of age, pharmaceutical companies are focusing increasingly on the quality of their screening collections. Storage conditions and their influence on compound stability and solubility are debated intensely. At Novartis, a strategy was developed that is different to most other companies: (1) comp...

journal_title：Combinatorial chemistry & high throughput screening

authors： Schopfer U,Engeloch C,Stanek J,Girod M,Schuffenhauer A,Jacoby E,Acklin P

更新日期：2005-09-01 00:00:00

abstract：:Substructural Molecular Fragments (SMF) method was applied for computer-aided design of new compounds potentially possessing high anti-HIV activities: tetrahydroimidazobenzodiazepinone (TIBO) derivatives and 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Using available experimental data, the SMF...

journal_title：Combinatorial chemistry & high throughput screening

authors： Varnek A,Solov'ev VP

更新日期：2005-08-01 00:00:00

abstract：:Recent studies have suggested that both constitutive androstane receptor (CAR) and pregnane X-receptor (PXR) are involved in the induction of rat liver microsomal cytochrome P-450 (CYP) 2B and 3A through a mechanism called cross-talk. In this study we intend to determine if a PXR-reporter gene assay could be used for ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Cui X,Thomas A,Montgomery D,Gu C,Morrison RA,White RE,Cheng KC

更新日期：2005-06-01 00:00:00

abstract：:The transmembrane metzinkin-proteases of the ADAM (a disintegrin and a metalloproteinase)-family ADAM10 and ADAM 17 are both implicated in the ectodomain shedding of various cell surface molecules including the IL6-receptor and the transmembrane chemokines CX3CL1 and CXCL16. These molecules are constitutively released...

journal_title：Combinatorial chemistry & high throughput screening

authors： Ludwig A,Hundhausen C,Lambert MH,Broadway N,Andrews RC,Bickett DM,Leesnitzer MA,Becherer JD

更新日期：2005-03-01 00:00:00

abstract：:The high level of attrition of drugs in clinical development has led pharmaceutical companies to increase the efficiency of their lead identification and development through techniques such as combinatorial chemistry and high-throughput (HTP) screening. Since the major reasons for clinical drug candidate failure other...

journal_title：Combinatorial chemistry & high throughput screening

authors： Shearer TW,Smith KS,Diaz D,Asher C,Ramirez J

更新日期：2005-02-01 00:00:00

abstract：:Normalization is an essential step in microarray data mining and analysis. For cDNA microarray data, the primary purpose of normalization is removing the intensity-dependent bias across different slides within an experimental group or between multiple groups. The locally weighted regression (lowess) procedure has been...

journal_title：Combinatorial chemistry & high throughput screening

authors： Wang J,Ma JZ,Li MD

更新日期：2004-12-01 00:00:00

abstract：:Chemical inhibitors have had a profound impact on many diverse fields of biology. The goal of chemical genetics is to use small molecules to perturb biological systems in a manner conceptually similar to traditional genetics. Key to the advancement of the chemical genetic paradigm is the further development of tools a...

journal_title：Combinatorial chemistry & high throughput screening

authors： Tochtrop GP,King RW

更新日期：2004-11-01 00:00:00

abstract：:Chromosome analysis has been a cornerstone both for the identification of genetic defects that predispose to a variety of genetic syndromes as well as for the analysis of cancer progression. The relatively low resolution of metaphase chromosomes, however, only allows characterization of major genetic events which are ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Cowell JK

更新日期：2004-09-01 00:00:00

abstract：:Structural genomics, structure-based analysis of gene products, has so far mainly concentrated on soluble proteins because of their less demanding requirements for overexpression, purification and crystallisation compared to membrane proteins. This so-called "low-hanging fruit" approach has generated more than 25,000 ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Lundstrom K

更新日期：2004-08-01 00:00:00

abstract：:Artificial neural networks (ANNs) have been applied for the quantitative structure-activity relationships (QSAR) studies of antibacterial activity against Escherichia coli, Serratia marcescens, Proteus vulgaris, Klebsiella pneumoniae and Pseudomonas aeruginosa of a large series of new imidazole derivatives. Antibacter...

journal_title：Combinatorial chemistry & high throughput screening

authors： Bucinski A,Markuszewski MJ,Wiktorowicz W,Krysinski J,Kaliszan R

更新日期：2004-06-01 00:00:00

abstract：:Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammator...

journal_title：Combinatorial chemistry & high throughput screening

authors： Wood SJ,Miller KA,David SA

更新日期：2004-05-01 00:00:00

abstract：:To meet growing needs for high throughput gene expression profiling, we established a new automated high throughput TaqMan RT-PCR method for quantitative mRNA expression analysis. In this method, the Allegro( trade mark ) (Zymark) system conducts all sample tracking and liquid handling steps, and ABI PRISM 7900 HT (Ap...

journal_title：Combinatorial chemistry & high throughput screening

authors： Pinhasov A,Mei J,Amaratunga D,Amato FA,Lu H,Kauffman J,Xin H,Brenneman DE,Johnson DL,Andrade-Gordon P,Ilyin SE

更新日期：2004-03-01 00:00:00

abstract：:Time-resolved fluorescence (TRF) assay formats are frequently used technologies in high-throughput screening. In this article, we have characterised the novel Plate::Vision(2) 96-microlens array reader (Carl Zeiss Jena GmbH, Germany) and compared it to the novel LEADseeker Generation IV multimodality imaging system (L...

journal_title：Combinatorial chemistry & high throughput screening

authors： Merk S,Lietz A,Kroner M,Valler M,Heilker R

更新日期：2004-02-01 00:00:00

abstract：:There is increasing evidence that redox regulation of transcription, particularly activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB), is important in inflammatory diseases. Human thioredoxin (TRX), a member of the oxidoreductase superfamily, was initially identified, as a factor which augments the produ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Eguchi M,McMillan M,Nguyen C,Teo JL,Chi EY,Henderson WR Jr,Kahn M

更新日期：2003-11-01 00:00:00

abstract：:Whole Cell-matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) is an emerging sensitive technique for rapid typing of microorganisms, efficient screening of biocombinatorial libraries of natural compounds and the analysis of complex biological samples, as whole cells, subcellula...

journal_title：Combinatorial chemistry & high throughput screening

authors： Vater J,Gao X,Hitzeroth G,Wilde C,Franke P

更新日期：2003-09-01 00:00:00

abstract：:The Nobel Prize in Chemistry 1902 was given to Hermann Emil Fischer "in recognition of the extraordinary services he had rendered by his work on sugar and purine synthesis". This truly great chemist of all time named a group of bicyclic nitrogenous structures as purines, discovered the synthesis of glucose, fructose a...

journal_title：Combinatorial chemistry & high throughput screening

authors： Franzén R,Tois J

更新日期：2003-08-01 00:00:00

abstract：:We have developed high throughput fluorescence cell imaging methods to screen chemical libraries for compounds with effects on diverse aspects of cell physiology. We describe screens for compounds that arrest cells in mitosis, that block cell migration, and that block the secretory pathway. Each of these screens yield...

journal_title：Combinatorial chemistry & high throughput screening

authors： Yarrow JC,Feng Y,Perlman ZE,Kirchhausen T,Mitchison TJ

更新日期：2003-06-01 00:00:00

abstract：:Calcium (Ca(2+)) fluoroionophores are useful in cell-based functional assays of G-protein coupled receptor (GPCR) activation or ion channel modulation. In this paper we describe new calcium probes that improve or overcome certain deficiencies in existing probes. These new fluoroionophores are based on acylation of ami...

journal_title：Combinatorial chemistry & high throughput screening

authors： Gee KR,Rukavishnikov A,Rothe A

更新日期：2003-06-01 00:00:00

abstract：:Single nucleotide polymorphisms (SNPs) are the most abundant variations in the human genome and have become the primary markers for genetic studies for mapping and identifying susceptible genes for complex diseases. Methods that genotype SNPs quickly and economically are of high values for these studies because they r...

journal_title：Combinatorial chemistry & high throughput screening

authors： Chen X

更新日期：2003-05-01 00:00:00

abstract：:We describe a high-throughput, quantitative technology for fast identification of all different clones present in selectively enriched phage surface-displayed cDNA libraries. The strategy is based on a combination of phage display and high-density arrays. To demonstrate the utility of the method cDNAs of Aspergillus f...

journal_title：Combinatorial chemistry & high throughput screening

authors： Kodzius R,Rhyner C,Konthur Z,Buczek D,Lehrach H,Walter G,Crameri R

更新日期：2003-03-01 00:00:00

abstract：:Screening of phage display libraries allows rapid identification of peptides binding to a target. However, functional analysis of the phage sequences and their reproduction as soluble and stable peptides are often the most time-consuming part in the screening. We have used here intein-based peptide biosynthesis to pro...

journal_title：Combinatorial chemistry & high throughput screening

authors： Björklund M,Valtanen H,Savilahti H,Koivunen E

更新日期：2003-02-01 00:00:00

abstract：:NMR has proven to be a valuable tool for identifying small molecule drug leads that serve as starting points for lead optimization programs. In addition, NMR screening can also be applied during lead optimization in order to improve the pharmacokinetic properties of a compound. In this paper we review the NMR methods ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Huth JR,Sun C

更新日期：2002-12-01 00:00:00

abstract：:A general procedure for the synthesis of a large variety of compounds comprising an alpha, beta,-unsaturated carbonyl functionality was developed. The use of one-pot cascade synthesis with (triphenylphosphora-nylidene)ethenone as a versatile reagent for various formations including heterocycles of different ring sizes...

journal_title：Combinatorial chemistry & high throughput screening

authors： Westmana J,Orrling K

更新日期：2002-11-01 00:00:00

abstract：:While the in vitro selection of nucleic acid binding species (aptamers) requires numerous liquid-handling steps, these steps are relatively straightforward and the overall process is therefore amenable to automation. Here we demonstrate that automated selection techniques are capable of generating aptamers against a n...

journal_title：Combinatorial chemistry & high throughput screening

authors： Cox JC,Rajendran M,Riedel T,Davidson EA,Sooter LJ,Bayer TS,Schmitz-Brown M,Ellington AD

更新日期：2002-06-01 00:00:00

abstract：:A method for producing tri- and tetrasubstituted ureas from carbamoyl imidazolium salts is presented. Carbamoyl imidazolium salts are prepared from the reaction of N,N carbonyldiimidazole (CDI) with secondary amines, followed by alkylation with iodomethane. These stable salts can be stored for extended periods and ar...

journal_title：Combinatorial chemistry & high throughput screening

authors： Batey RA,Shen M,Santhakumar V,Yoshina-Ishii C

更新日期：2002-05-01 00:00:00

abstract：:It is practically impossible in a short period of time to synthesize and test all compounds in any large exhaustive chemical library. We discuss rational approaches to selecting representative subsets of virtual libraries that help direct experimental synthetic efforts for both targeted and diverse library design. For...

journal_title：Combinatorial chemistry & high throughput screening

authors： Tropsha A,Zheng W

更新日期：2002-03-01 00:00:00

abstract：:A pulsed ultrafiltration-mass spectrometric screening method has been developed to evaluate the metabolic stability of drugs. Pooled human liver microsomes containing cytochrome P450 enzymes were trapped by an ultrafiltration membrane in a stirred flow-through chamber, and eight beta-blocker drugs including acebutolol...

journal_title：Combinatorial chemistry & high throughput screening

authors： Geun Shin Y,Bolton JL,van Breemen RB

更新日期：2002-02-01 00:00:00

abstract：:This review describes computational procedures for deriving the amino acid sequences that are compatible with a given protein backbone structure. Such procedures can be used to gain insight into the constraints imposed by the 3D structure of the protein sequence, or to design proteins that are likely to adopt a given ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Jaramillo A,Wernisch L,Hery S,Wodak SJ

更新日期：2001-12-01 00:00:00

abstract：:Combinatorial phage peptide libraries have been used to identify the ligands for specific target molecules. These libraries are also useful for identification of the specific substrates of various proteases. A substrate phage library has a random peptide sequence at the N-terminus of the phage coat protein and an addi...

journal_title：Combinatorial chemistry & high throughput screening

authors： Ohkubo S,Miyadera K,Sugimoto Y,Matsuo K,Wierzba K,Yamada Y

更新日期：2001-11-01 00:00:00

abstract：:This review describes the design process from conception through realisation and optimisation of a minibody'--a minimised antibody. The result was a proteinaceous molecule of novel fold and metal binding activity. We explain how combinatorial approaches, using phage display libraries, were used to randomise loop regio...

journal_title：Combinatorial chemistry & high throughput screening

authors： Vaughan CK,Sollazzo M

更新日期：2001-08-01 00:00:00

abstract：:Drug metabolism can have profound effects on the pharmacological and toxicological profile of therapeutic agents. In the pharmaceutical industry, many in vitro techniques are in place or under development to screen and optimize compounds for favorable metabolic properties in the drug discovery phase. These in vitro te...

journal_title：Combinatorial chemistry & high throughput screening

authors： Masimirembwa CM,Thompson R,Andersson TB

更新日期：2001-05-01 00:00:00

abstract：:Shotgun phage display cloning is a useful tool for studying interactions between bacterial and host proteins. Libraries are constructed by cloning randomly fragmented prokaryotic DNA into phage mid-vectors. Theoretically, these libraries will consist of phages that together display all proteins encoded by the bacteria...

journal_title：Combinatorial chemistry & high throughput screening

authors： Jacobsson K,Frykberg L

更新日期：2001-04-01 00:00:00

abstract：:Approximately 5-10% of all colorectal carcinomas arise from cancer predisposition syndromes caused by heterozygote germline mutations in post-replicative DNA mismatch repair (MMR) genes. In contrast to gastrointestinal polyposis syndromes, carcinomas in these patients do not occur on the background of increased number...

journal_title：Combinatorial chemistry & high throughput screening

authors： Merkelbach-Bruse S,Köse S,Losen I,Bosserhoff AK,Buettner R

更新日期：2000-12-01 00:00:00

abstract：:A simple and fast method with high reliability is necessary for the identification of mutations, polymorphisms and sequence variants (MPSV) within many genes and many samples, e.g. for clarifying the genetic background of individuals with multifactorial diseases. Here we review our experience with the polymerase chain...

journal_title：Combinatorial chemistry & high throughput screening

authors： Miterski B,Krüger R,Wintermeyer P,Epplen JT

更新日期：2000-06-01 00:00:00

abstract：:Polymer-bound triphenylphosphine can replace triphenylphosphine in the Mitsunobu reaction to generate stereochemically inverted secondary alcohols. This method is comparable with the standard Mitsunobu reaction in terms of inversion of stereochemistry, yield, and reaction time, even for sterically very hindered second...

journal_title：Combinatorial chemistry & high throughput screening

authors： White JM,Tunoori AR,Dutta D,Georg GI

更新日期：2000-04-01 00:00:00

abstract：:Genetic mutations/polymorphisms analyses play a great role in genetic and medical research, and clinical diagnosis. Most conventional methods for genetic assay are based on slab gel electrophoresis that is both labor-intensive and time-consuming. Recently, capillary electrophoresis (CE) has been used for genetic analy...

journal_title：Combinatorial chemistry & high throughput screening

authors： Ren J

更新日期：2000-02-01 00:00:00

abstract：:Two approaches were utilized to increase the throughput of pulsed ultrafiltration assays of ligand binding to human serum albumin, reducing the volume of the ultrafiltration chamber and combining pulsed ultrafiltration with high performance liquid chromatography-atmospheric pressure chemical ionization mass spectromet...

journal_title：Combinatorial chemistry & high throughput screening

authors： Gu C,Nikolic D,Lai J,Xu X,van Breemen RB

更新日期：1999-12-01 00:00:00

abstract：:High performance liquid chromatography (HPLC), electrospray ionization mass spectrometry (ESI) and high performance liquid chromatography coupled to mass spectrometry (LC-MS) were used to analyze randomly chosen samples from parallel syntheses carried out on derivatized polypropylene crowns compatible with a Multipin ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Aubagnac JL,Amblard M,Enjalbal C,Subra G,Martinez J,Durand P,Renaut P

更新日期：1999-10-01 00:00:00

abstract：:Phage display is a biological system which facilitates the cloning and rapid selection of peptides from large combinatorial libraries. In compa-rison to the chemical combinatorial approach, the advantages of phage display lie in its simplicity and replicability. While phage display has many diverse applications, this ...

journal_title：Combinatorial chemistry & high throughput screening

authors： Andres CJ,Denhart DJ,Deshpande MS,Gillman KW

更新日期：1999-08-01 00:00:00