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 journalArticle

6 Citations (Scopus)

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

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Glycoproteins
Acids
Conformations
Phosphotransferases
NAD(P)H Dehydrogenase (Quinone)
Gastrointestinal Stromal Tumors
Molecules
Molecular modeling
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein Binding
Protein-Tyrosine Kinases
Blood Proteins
Tumors
X-Rays
X rays
Imatinib Mesylate

Keywords

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

Cite this

Characterization of binding mode of imatinib to human α 1-acid glycoprotein. / Fitos, I.; Simon, Á; Zsila, F.; Mády, G.; Bencsura, Á; Varga, Z.; orfi, L.; Kéri, G.; Visy, J.

In: International Journal of Biological Macromolecules, Vol. 50, No. 3, 01.04.2012, p. 788-795.

Research output: Contribution to journalArticle

Fitos, I, Simon, Á, Zsila, F, Mády, G, Bencsura, Á, Varga, Z, orfi, L, Kéri, G & Visy, J 2012, 'Characterization of binding mode of imatinib to human α 1-acid glycoprotein', International Journal of Biological Macromolecules, vol. 50, no. 3, pp. 788-795. https://doi.org/10.1016/j.ijbiomac.2011.11.023
Fitos, I. ; Simon, Á ; Zsila, F. ; Mády, G. ; Bencsura, Á ; Varga, Z. ; orfi, L. ; Kéri, G. ; Visy, J. / Characterization of binding mode of imatinib to human α 1-acid glycoprotein. In: International Journal of Biological Macromolecules. 2012 ; Vol. 50, No. 3. pp. 788-795.
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