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We describe the parallel synthesis and in vitro evaluation of a cationic polymer library for the discovery of nonviral gene delivery vectors. The library was synthesized based on the ring-opening polymerization reaction between epoxide groups of diglycidyl ethers and the amines of (poly)amines. Parallel screening of soluble library constituents led to the(More)
Methotrexate from various commercial sources has been found to contain 0.5 to 48% (w/w) of the enantiomer D-methotrexate. The two methotrexate enantiomers were separated by using chiral high-performance liquid chromatography with an octadecyl silica column and a mobile phase containing L-proline and cupric nitrate. For the assay of D-methotrexate impurity(More)
A robotic high-throughput displacer screen was developed and employed to identify chemically selective displacers for several protein pairs in cation exchange chromatography. This automated screen enabled the evaluation of a wide range of experimental conditions in a relatively short period of time. Displacers were evaluated at multiple concentrations for(More)
Quantitative Structure-Retention Relationship (QSRR) models are developed for the prediction of protein retention times in anion-exchange chromatography systems. Topological, subdivided surface area, and TAE (Transferable Atom Equivalent) electron-density-based descriptors are computed directly for a set of proteins using molecular connectivity patterns and(More)
Although recent advances in multimodal chromatography have shown significant potential for selective protein purification, there is a need to establish a deeper understanding of the nature of selectivity in these systems. In this work, the adsorption behavior of a library of commercially available proteins with varying physicochemical properties was(More)
This study examines protein adsorption behavior and the effects of mobile phase modifiers in multimodal chromatographic systems. Chromatography results with a diverse protein library indicate that multimodal and ion exchange resins have markedly different protein binding behavior and selectivity. NMR results corroborate the stronger binding observed for the(More)
A protein library exhibiting a range of properties was employed to study protein binding behavior in hydroxyapatite systems. Chromatographic retention on ceramic hydroxyapatite (CHT) chromatography was determined using a sodium chloride gradient in the presence of different phosphate concentrations. Results from the column experiments were then analyzed(More)
A quantitative structure-property relationship (QSPR) modeling approach was employed to correlate the physicochemical properties and structural components of multi-modal ion-exchange ligands with their ability to bind proteins under high-salt conditions. These ion-exchange ligands contain various substructures, which may contribute to secondary interactions(More)
The ability to predict downstream protein purification processes is of great value in the biopharmaceutical industry; saving time, cost and resources. While many complex models exist, the appropriate use of simple models can be a useful tool for rapidly designing and optimizing processes as well as for risk analysis and establishing parameter ranges. In(More)
The effect of an alternate strategy employing two different flowrates during loading was explored as a means of increasing system productivity in Protein-A chromatography. The effect of such a loading strategy was evaluated using a chromatographic model that was able to accurately predict experimental breakthrough curves for this Protein-A system. A(More)