A two-state model for the kinetics of competitive radioligand binding

Author(s):
Guo, D. (0000-0001-6142-4825); Peletier, L.A.; Bridge, L.; Keur, W.; Vries, H. de; Zweemer, J.M. (0000-0002-3539-3129); Heitman, L.H. (0000-0002-1381-8464); IJzerman, A.P. (0000-0002-1182-2259)
Published
2018
Publication type
Article / Letter to editor

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

Kinetics, protein binding, modelling
Date issued
2018-05-31
Language
English
Is part of
British Journal of Pharmacology (2018), Vol. 175, no. 10, p. 1719-1730
hdl
1887/65136
doi
10.1111/bph.14184