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A competition between hydrophobic and electrostatic interactions in protein–ligand systems. Binding of heterogeneously halogenated benzotriazoles by the catalytic subunit of human protein kinase CK2

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dc.abstract.en<p>A series of chlorine-substituted benzotriazole derivatives, representing all possible substitution patterns of halogen atoms attached to the benzotriazole benzene ring, were synthetized as potential inhibitors of human protein kinase CK2. Basic ADME parameters for the free solutes (hydrophobicity, electronic properties) together with their binding affinity to the catalytic subunit of protein kinase CK2 were determined with reverse-phase HPLC, spectrophotometric titration, and Thermal Shift Assay Method, respectively. The analysis of position-dependent thermodynamic contribution of a chlorine atom attached to the benzotriazole ring confirmed the previous observation for brominated benzotriazoles, in which substitution at positions 5 and 6 with bromine was found crucial for ligand binding. In all tested halogenated benzotriazoles the replacement of Br with Cl decreases the hydrophobicity, while the electronic properties remain virtually unaffected. Supramolecular architecture identified in the just resolved crystal structures of three of the four possible dichloro-benzotriazoles shows how substitution distant from the triazole ring affects the pattern of intermolecular interactions. Summarizing, the benzotriazole benzene ring substitution pattern has been identified as the main driver of ligand binding, predominating the non-specific hydrophobic effect.</p>
dc.affiliationUniwersytet Warszawski
dc.contributor.authorPoznański, Jarosław
dc.contributor.authorMarzec, Ewa
dc.contributor.authorMieczkowska, Kinga
dc.contributor.authorWoźniak, Krzysztof
dc.contributor.authorTrzybiński, Damian
dc.contributor.authorMaciejewska, Agnieszka
dc.contributor.authorBretner, Maria
dc.contributor.authorKasperowicz, Sławomir
dc.date.accessioned2024-01-24T17:18:16Z
dc.date.available2024-01-24T17:18:16Z
dc.date.issued2020
dc.description.financePublikacja bezkosztowa
dc.description.number6
dc.description.volume72
dc.identifier.doi10.1002/IUB.2271
dc.identifier.issn1521-6543
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/101479
dc.identifier.weblinkhttps://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.2271
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofIUBMB Life
dc.relation.pages1211-1219
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enbromobenzotriazoles chlorobenzotriazoles chromatographic hydrophobicity index crystal structure halogenated benzotriazoles human protein kinase CK2 thermal shift assay
dc.titleA competition between hydrophobic and electrostatic interactions in protein–ligand systems. Binding of heterogeneously halogenated benzotriazoles by the catalytic subunit of human protein kinase CK2
dc.typeJournalArticle
dspace.entity.typePublication