1. A two-state model for the kinetics of competitive radioligand binding
- Author
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Wesley Keur, Dong Guo, Annelien J.M. Zweemer, Henk de Vries, Laura H. Heitman, Lloyd Bridge, Lambertus A. Peletier, and Adriaan P. IJzerman
- Subjects
0301 basic medicine ,Pharmacology ,State model ,Chemistry ,Ligand ,Kinetics ,Plasma protein binding ,Radioligand Assay ,Receptor–ligand kinetics ,03 medical and health sciences ,030104 developmental biology ,Radioligand ,Biophysics ,Receptor - Abstract
Ligand-receptor binding kinetics is receiving increasing attention in the drug research community. The Motulsky and Mahan model, a one-state model, offers a method for measuring the binding kinetics of an unlabelled ligand, with the assumption that the labelled ligand has no preference while binding to distinct states or conformations of a drug target. As such, the one-state model is not applicable if the radioligand displays biphasic binding kinetics to the receptor. receptor ligands. In addition, limitations of the model were investigated as well. H]-NECA was used. The model was further validated by good correlation between simulated results and the experimental data. The two-state model is sufficient to analyse the binding kinetics of an unlabelled ligand, when a radioligand shows biphasic association characteristics. We expect this two-state model to have general applicability for other targets as well. BACKGROUND AND PURPOSE EXPERIMENTAL APPROACH KEY RESULTS CONCLUSION
- Published
- 2018