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Title: | Binding of the anticancer drug BI-2536 to human serum albumin. A spectroscopic and theoretical study |
Author: | Fernandez-Sainz, Jesús Pacheco-Linan, Pedro J. Granadino Roldán, José M. Bravo, Ivan Garzón, Andrés Rubio Martínez, Jaime Albaladejo, Jose |
Keywords: | Medicaments antineoplàstics Albúmines Fixació de proteïnes Antineoplastic agents Albumins Protein binding |
Issue Date: | 1-Jul-2017 |
Publisher: | Elsevier B.V. |
Abstract: | BI-2536 is a potent Polo-like kinase inhibitor which induces apoptosis in diverse human cancer cell lines. The binding affinity of BI-2536 for human serum albumin (HSA) protein may define its pharmacokinetic and pharmacodynamic profile. We have studied the binding of BI-2536 to HSA by means of different spectroscopic techniques and docking calculations. We have experimentally observed that the affinity of BI-2536 for HSA is higher than that of other common HSA binding drugs. Therefore, it can be postulated that the drug dose should be increased to achieve a certain concentration of free drug in plasma, although BI-2536 could also reach tumour tissues by uptaking HSA/BI-2536 complex. Only a single binding site on HSA has been observed for BI-2536 which seems to correspond to the subdomain IIA pocket. The formation of the HSA/BI-2536 complex is a spontaneous and entropy-driven process that does not cause a significant change of the secondary structure of the protein. Its endothermic character could be related to proton release. Thermodynamic analysis showed that the main protein-drug interactions are of the van der Waals type although the presence of amide and ether groups in BI-2536 could also allow H-bonding with some residues in the subdomain IIA pocket. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.jphotobiol.2017.05.016 |
It is part of: | Journal of Photochemistry and Photobiology B-Biology, 2017, vol. 172, p. 77-87 |
URI: | http://hdl.handle.net/2445/187566 |
Related resource: | https://doi.org/10.1016/j.jphotobiol.2017.05.016 |
ISSN: | 1011-1344 |
Appears in Collections: | Articles publicats en revistes (Ciència dels Materials i Química Física) |
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