Characterization of binding mode of imatinib to human α 1-acid glycoprotein

I. Fitos, Á Simon, F. Zsila, G. Mády, Á Bencsura, Z. Varga, L. orfi, G. Kéri, J. Visy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)788-795
Number of pages8
JournalInternational Journal of Biological Macromolecules
Volume50
Issue number3
DOIs
StatePublished - Apr 1 2012

Keywords

  • Fluorescence quenching
  • Genetic variants
  • Imatinib
  • Induced circular dichroism
  • Protein binding
  • α -Acid glycoprotein

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