Combinatorial Chemistry & High Throughput Screening - Volume 14, Issue 1, 2011

The drug discovery landscape is at cross roads with profound changes looming in the horizon. Open innovation has become the new ‘mantra’ for reinvigorating the pharmaceutical R&D's lackluster drug candidate pipeline. To fill this void, academia has now ventured from its traditional role of exploring the fundamental aspects of disease biology in to the high throughput screening arena in a big way. Thanks to the NIH Roadma Read More

An efficient synthesis of stable phosphonate ylides and phosphonate esters is described via a one-pot reaction between activated acetylenes and triphenylphosphite in the presence of sulfonamides and heterocyclic NH-acids. Single X-ray diffraction analysis and NMR studies were used in characterizing the ylides and phosphonate ester products. Dynamic NMR studies performed on a phosphonate ylide allowed the calculati Read More

Bacteriophage (phage) display has been exploited for the purpose of discovering new cancer specific targeting peptides. However, this approach has resulted in only a small number of tumor targeting peptides useful as in vivo imaging agents. We hypothesize that in vivo screening for tumor uptake of fluorescently tagged phage particles displaying multiple copies of an in vivo selected tumor targeting peptide will expedite the Read More

This paper describes a stripping method for the determination of nevirapine at the submicromolar concentration levels The method is based on controlled adsorptive accumulation of nevirapine at thin-film mercury electrode, followed by a linear cyclic scan voltammetry measurement of the surface species. Optimal experimental conditions include a 2.0 × 10-3 mol L-1 NaOH solution (supporting electrolyte), an accumulation Read More

This paper reports on a systematic method - called PLUXter - developed for screening and data mining of large numbers of potential metal-organic framework compounds that have been synthesized then subsequently analyzed with high throughput synchrotron radiation X-ray powder diffraction. The first part of the method utilizes principal components analysis (PCA), which allows materials to be ranked in order of crys Read More

OPLS discriminant analysis (OPLS-DA) was successfully applied for the selection of a limited number of gene transcripts necessary to discriminate PTPN11 and RAS mutated cells in acute lymphoblastic leukaemia (ALL) patients. The original set of 273 variables with VIP (1) values higher than 2.0 in the OPLS-DA model could be further reduced to 200 by elimination of less informative variables in the PCA class models adopted for S Read More

A panel of luminescent Saccharomyces cerevisiae cell-based nuclear receptor assays, consisting of human estrogen receptors α and β, androgen receptor, and aryl hydrocarbon receptor, was miniaturized from the standard 96-well microplate format to high throughput 384- and 1536-well microplate formats. In these assays, firefly luciferase lacking the peroxisome targeting sequence was used as a reporter and D-luciferin Read More

A compartmentalized tyramide labeling system (CoaTi) employing flow cytometry for sorting of yeast cells was developed as ultrahigh throughput screening for Glucose oxidase (GOx) from Aspergillus niger. CoaTi combines in vitro compartmentalization technology with the CARD reporter system which uses fluorescein tyramide labels for detection of peroxidase activity. Physical connection between cells and fluorescein tyr Read More

In this paper we propose a matrix depiction and two new invariants of DNA sequences. This approach is illustrated on the primate mitochondrial DNA sequences for 11 different species and 80 different H5N1 avian influenza virus DNA sequences. We also construct the dendrogram tree for them. These phylogenies obtained are generally consistent with evolutionary trees constructed in previous studies.