Universal quantitative detection without the need for analyte reference standards would offer substantial benefits in many areas of analytical science. The quantitative capability of high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) was investigated for 50 compounds with a wide range of physical and chemical properties. It is widely believed that CAD is a mass detector.
View Article and Find Full Text PDFOne of the key challenges facing early stage drug discovery is understanding the commonly observed difference between the activity of compounds in biochemical assays and cellular assays. Traditionally, indirect or estimated cell permeability measurements such as estimations from logP or artificial membrane permeability are used to explain the differences. The missing link is a direct measurement of intracellular compound concentration in whole cells.
View Article and Find Full Text PDFUnderstanding the quality of a screening collection is the first step to improving it and, as a result, the quality of the screening process. This article outlines how this issue was approached at GlaxoSmithKline and some of the hurdles that needed to be overcome to achieve success. The article focuses specifically on the necessary software and hardware infrastructure needed, and at some of the extra benefits of such a project in terms of data mining and data modelling.
View Article and Find Full Text PDFPre-protein sequence data was used to design substrates for SpsB, the bacterial signal peptidase I enzyme from Staphylococcus aureus. Key elements were an alkyl membrane anchor, proline at P5 and lysine at P2. The proline at P5 induced a helical turn in the lipopeptide, as deduced from NMR studies, from P6 to P2 in membrane mimetic solvents.
View Article and Find Full Text PDFA series of novel inhibitors of lipoprotein associated phospholipase A2 were isolated from the culture broths of Pseudomonas fluorescens strain DSM11579. The inhibitors fall into two structurally isomeric classes each of which comprise compounds incorporating glycosylated hydrocarbon chains. The structure elucidation for the major member of each structural class is reported.
View Article and Find Full Text PDF