Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8335090 | International Journal of Biological Macromolecules | 2012 | 8 Pages |
Abstract
Imatinib (IMT) is a selective tyrosine kinase inhibitor, used in the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Its strong plasma protein binding was found to belong to the F1*S genetic variant of α1-acid glycoprotein (AGP). In this work, comparative AGP binding studies were performed with IMT fragment molecules to reveal which parts of the molecule are important in the high-affinity interaction provoking specific spectral changes. Molecular modeling calculations indicated that IMT docked into the X-ray structure of AGP/F1 adopts a bent, compact conformation. This binding mode is similar to those found in its complexes with some low-affinity kinases and a quinone reductase, being strikingly different from the extended conformation of IMT in its high-affinity kinase targets.
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Authors
I. Fitos, Á. Simon, F. Zsila, G. Mády, Á. Bencsura, Z. Varga, L. Årfi, G. Kéri, J. Visy,