TY - JOUR
T1 - Characterization of binding mode of imatinib to human α1-acid glycoprotein
AU - Fitos, I.
AU - Simon, Á
AU - Zsila, F.
AU - Mády, G.
AU - Bencsura, Á
AU - Varga, Z.
AU - orfi, L.
AU - Kéri, G.
AU - Visy, J.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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.
AB - 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.
KW - Fluorescence quenching
KW - Genetic variants
KW - Imatinib
KW - Induced circular dichroism
KW - Protein binding
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U2 - 10.1016/j.ijbiomac.2011.11.023
DO - 10.1016/j.ijbiomac.2011.11.023
M3 - Article
C2 - 22142793
AN - SCOPUS:84857793512
SN - 0141-8130
VL - 50
SP - 788
EP - 795
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
IS - 3
ER -