Characterization of heterogeneity of biomolecular interactions using 3rd generation biosensor

Detta är en Kandidat-uppsats från KTH/Skolan för kemivetenskap (CHE)

Sammanfattning: A new tool for kinetic evaluation of kinetic rate constants is enabled by a 3rd generation biosensor. The tool is developed to meet the need of reliably experimental information and communication between pharmaceutical companies and regulatory agencies to increase the productivity and decrease the associated risks. Too obtain the necessary competences and resources for this, a project consisting of Attana AB, AstraZeneca AB, Waters Nordic AB and Karlstad University was established. The main aim of the project is to achieve a comprehension understanding of interactions of different character e.g. fast and slow kinetics. This report concerns a fast interaction system. By analyzing a parathyroid hormone system using standard biosensor assays and single cycle kinetics with Attana Cell™ 200 instruments the fast interaction was characterized. The experimental data was analyzed using standard kinetic evaluation and an adaptive interaction distribution algorithm. The latter tool is developed at Karlstad university in order to describe the heterogeneity of interactions. The idea is to use the heterogeneity information as a decision support in drug development. A sub aim was to investigate the feasibility of the single cycle kinetic assays compared to the standard biosensors assays. The results shows a decrease of experimental time by 70% for homogene interaction and the protocol enables assay without or with less regeneration.

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