Characterization of binding mode of imatinib to human α1-acid glycoprotein.

TitleCharacterization of binding mode of imatinib to human α1-acid glycoprotein.
Publication TypeJournal Article
Year of Publication2012
AuthorsFitos, I, Simon, Á, Zsila, F, Mády, G, Bencsura, Á, Varga, Z, Orfi, L, Kéri, G, Visy, J
JournalInt J Biol Macromol
Date Published2012 Apr 1
KeywordsBenzamides, Humans, Imatinib Mesylate, Models, Molecular, Orosomucoid, Piperazines, Protein Binding, Protein Conformation, Protein Kinase Inhibitors, Pyrimidines, Spectrum Analysis

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 α(1)-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.

Alternate JournalInt. J. Biol. Macromol.
PubMed ID22142793