Thermodynamic parameters for binding of some halogenated inhibitors of human protein kinase CK2
PBN-AR
Instytucja
Wydział Chemiczny (Politechnika Warszawska)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Biochemical and Biophysical Research Communications
ISSN
0006-291X
EISSN
Wydawca
DOI
URL
Rok publikacji
2015
Numer zeszytu
1
Strony od-do
282-287
Numer tomu
456
Identyfikator DOI
Liczba arkuszy
0.5
Autorzy
(liczba autorów: 7)
Pozostali autorzy
+ 5
Autorzy przekładu
(liczba autorów przekładu: 0)
Słowa kluczowe
en
Protein kinase CK2; Bromobenzotriazoles; Bromobenzimidazoles; Halogenated protein ligands; DSC; Fluorescence
Streszczenia
Język
en
Treść
Abstract The interaction of human CK2α with a series of tetrabromobenzotriazole (TBBt) and tetrabromobenzimidazole (TBBz) analogs, in which one of the bromine atoms proximal to the triazole/imidazole ring is replaced by a methyl group, was studied by biochemical (IC50) and biophysical methods (thermal stability of protein–ligand complex monitored by DSC and fluorescence). Two newly synthesized tri-bromo derivatives display inhibitory activity comparable to that of the reference compounds, TBBt and TBBz, respectively. DSC analysis of the stability of protein–ligand complexes shows that the heat of ligand binding (Hbind) is driven by intermolecular electrostatic interactions involving the triazole/imidazole ring, as indicated by a strong correlation between Hbind and ligand pKa. Screening, based on fluorescence-monitored thermal unfolding of protein–ligand complexes, gave comparable results, clearly identifying ligands that most strongly bind to the protein. Overall results, additionally supported by molecular modeling, confirm that a balance of hydrophobic and electrostatic interactions contribute predominantly, relative to possible intermolecular halogen bonding, in binding of the ligands to the CK2α ATP-binding site.
Inne
System-identifier
WUT279f61802d884a209c706c9d97c40183
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