Quantification Of Complex Mixtures Research Articles

Finding the Right Candidate for the Right Position: A Fast NMR-Assisted Combinatorial Method for Optimizing Nucleic Acids Binders.

Development of strong and selective binders from promiscuous lead compounds represents one of the most expensive and time-consuming tasks in drug discovery. We herein present a novel fragment-based combinatorial strategy for the optimization of multivalent polyamine scaffolds as DNA/RNA ligands. Our protocol provides a quick access to a large variety of regioisomer libraries that can be tested for selective recognition by combining microdialysis assays with simple isotope labeling and NMR experiments. To illustrate our approach, 20 small libraries comprising 100 novel kanamycin-B derivatives have been prepared and evaluated for selective binding to the ribosomal decoding A-Site sequence. Contrary to the common view of NMR as a low-throughput technique, we demonstrate that our NMR methodology represents a valuable alternative for the detection and quantification of complex mixtures, even integrated by highly similar or structurally related derivatives, a common situation in the context of a lead optimization process. Furthermore, this study provides valuable clues about the structural requirements for selective A-site recognition.

Identification and determination of chlorinated paraffins using multivariate evaluation of gas chromatographic data

Chlorinated paraffins (CPs) were found in the biodegradable fraction of source separated waste from Uppsala, Sweden. We identified and quantified the CPs by multivariate evaluation of gas chromatography-electron capture detection chromatograms. Using principal component analyses (PCA) we identified different types of CP-formulations and also obtain quantitative data. PCA yielded better identifications of individual CP-formulations than visual comparison of chromatograms. Partial least squares regression gave good calibration curves of the standards, but did not work for the waste samples. No source of CPs could be identified in the waste collection chain, and as the waste samples seemed to contain at least two different CP-formulations the source was probably to be found in the waste material itself. The method was used to determine CPs in additional environmental samples, demonstrating that multivariate methods may be developed into a powerful tool for identification and quantification of complex mixture.