caa a22 4500 605506884 CHVBK 20210128100629.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00775-014-1211-9 doi (NATIONALLICENCE)springer-10.1007/s00775-014-1211-9 Interaction of the anticancer gallium(III) complexes of 8-hydroxyquinoline and maltol with human serum proteins [Elektronische Daten] [Éva Enyedy, Orsolya Dömötör, Krisztina Bali, Anasztázia Hetényi, Tiziano Tuccinardi, Bernhard Keppler] Tris(8-quinolinolato)gallium(III) (KP46) and tris(maltolato)gallium(III) (GaM) are promising orally active antitumor metallodrugs currently undergoing clinical trials. Their interaction with human serum albumin (HSA) and transferrin (Tf) was studied in detail in aqueous solution by the combination of various methods such as spectrofluorometry, UV-vis spectrophotometry, 1H and saturation transfer difference NMR spectroscopy, and ultrafiltration-UV-vis spectrophotometry. Binding data were evaluated quantitatively. Tf was found to replace the original ligand much less efficiently in KP46 than in GaM, whereas a significant noncovalent binding of KP46 with HSA (log K′=4.04) retaining the coordination environment around gallium(III) was found. The interaction between HSA and KP46 was also confirmed by protein-complex modeling calculations. On the basis of the conditional stability constants, the distribution of gallium(III) in serum was computed and compared for these metallodrugs under physiological conditions, and revealed the prominent role of HSA in the case of KP46 and that of Tf for GaM. Graphical abstract: SBIC, 2014 Solution equilibrium nationallicence Albumin nationallicence Transferrin nationallicence Binding affinity nationallicence Fluorescence nationallicence apoTf : Apotransferrin nationallicence GaM : Tris(3-hydroxy-2-methyl-4H-pyran-4-onato)gallium(III) nationallicence HEPES : 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid nationallicence HMM : High molecular mass nationallicence HSA : Human serum albumin nationallicence HQ : 8-Hydroxyquinoline nationallicence KP46 : Tris(8-quinolinolato)gallium(III) nationallicence LMM : Low molecular mass nationallicence PDB : Protein Data Bank nationallicence STD : Saturation transfer difference nationallicence Tf : Human serum transferrin nationallicence Enyedy Éva Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary aut Dömötör Orsolya Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary aut Bali Krisztina Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary aut Hetényi Anasztázia Department of Medical Chemistry, University of Szeged, Dóm tér 8, 6720, Szeged, Hungary aut Tuccinardi Tiziano Department of Pharmacy, University of Pisa, 56126, Pisa, Italy aut Keppler Bernhard Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/1(2015-01-01), 77-88 0949-8257 20:1<77 2015 20 775 https://doi.org/10.1007/s00775-014-1211-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-014-1211-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Enyedy Éva Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary aut NATIONALLICENCE 700 1- Dömötör Orsolya Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary aut NATIONALLICENCE 700 1- Bali Krisztina Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary aut NATIONALLICENCE 700 1- Hetényi Anasztázia Department of Medical Chemistry, University of Szeged, Dóm tér 8, 6720, Szeged, Hungary aut NATIONALLICENCE 700 1- Tuccinardi Tiziano Department of Pharmacy, University of Pisa, 56126, Pisa, Italy aut NATIONALLICENCE 700 1- Keppler Bernhard Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/1(2015-01-01), 77-88 0949-8257 20:1<77 2015 20 775