Tag Archives: protein kinase CK2

Search of protein kinase CK2 inhibitors based on purine-2,6-diones derivatives

M. V. Protopopov1, O. V. Ostrynska2, D. H. Ivanchenko3, S. A. Starosyla2,
V. G. Bdzhola2, M. I. Romanenko3, S. M. Yarmoluk2

1Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: mykola.protopopov@gmail.com;
2Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
e-mail: sergiy@yarmoluk.org.ua;
3Zaporozhye State Medical University, Ukraine;
e-mail: ivanchenko230181@gmail.com

This work is aimed to the search of protein kinase CK2 inhibitors among the purine-2,6-dione derivatives by molecular docking and biochemical tests. It was found that the most active compound 8-[2-[(3-methoxyphenyl)methylidene]hydrazine-1-yl]-3-methyl-7-(3-phenoxypropyl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione inhibited protein kinase CK2 with IC50 value of 8.5 µM in vitro in kinase assay. Biochemical tests and computer simulation results allowed determining the binding mode of the most active compound and structure-activity relationships.

Participation of proteinkinase CK2 in regulation of human erythrocytes plasma membrane redox system activity: relative contribution of Са(2+)-dependent and Са(2+)-independent mechanisms of its activation

I. N. Iakovenko, V. V. Zhirnov, A. P. Kozachenko,
O. V. Shablykin, V. S. Brovarets

Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: brovarets@bpci.kiev.ua

Involvement of protein kinase CK2 ( in modulation of live cells trans-plasma membrane electron transport was first discovered. Using human erythrocytes a decrease of plasma membrane redox system (PMRS) activity is shown under the action of specific protein kinase CK2 inhibitors.
Using inhibitory analysis the activity regulation of human erythrocytes PMRS by Ca2+-dependent and Ca2+-independent mechanisms were investigated. It was shown that functional Ca2+-antagonists (nitrendipine and calmidazolium) significantly increased, and functional Ca2+-agonists to some extent reduced (calcimycin) or did not affect (Bay K 8644) the trans-plasma membrane electron transport in these cells. In all cases of calcium signaling the system modifications inhibition of kinase CK2 is also accompanied by significant reductions of erythrocytes PMRS activity. Against the background of kinase CK2 inhibition the mentioned influence activity of nitrendipine and Bay K 8644 on PMRS does not change, that of calmidazolium increases and of calcimycin is not revealed. Obtained results demonstrate the inhibitory effect of Ca2+ and calmodulin on human erythrocytes PMRS and the activation of this system by protein kinase CK2 mainly through Ca2+-independent mechanisms. Some participation of calmodulin in PMRS activity regulation by kinase CK2 is discussed.