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Thermodynamic contribution of iodine atom to the binding of heterogeneously polyhalogenated benzotriazoles by the catalytic subunit of human protein kinase CK2
Author(s) -
Marzec Ewa,
Poznański Jarosław,
Paprocki Daniel
Publication year - 2020
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2257
Subject(s) - chemistry , benzotriazole , halogen , ligand (biochemistry) , ring (chemistry) , protein subunit , benzene , protein kinase a , catalysis , iodine , stereochemistry , crystallography , organic chemistry , enzyme , biochemistry , alkyl , receptor , gene
A series of novel benzotriazole derivatives containing iodine atom(s) were synthesized. The binding of these compounds to the catalytic subunit of human protein kinase CK2 was evaluated using differential scanning fluorimetry. The obtained thermodynamic data were compared with those determined previously for the brominated and chlorinated benzotriazole analogues to get a deeper insight into the thermodynamic contribution of iodine substitution to the free energy of ligand binding. We have shown that iodine atom(s) attached to the benzene ring of benzotriazole enhance(s) its binding by the target protein. This effect is the strongest when two iodine atoms are attached at positions peripheral to the triazole ring, which according to the structures deposited in protein data bank may be indicative for the formation of the halogen bond between iodine and carbonyl groups of residues located in the hinge region of the protein. Finally, quantitative structure–activity relationship analysis pointed the solute hydrophobicity as the main factor contributing to the binding affinity.