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Design of CK2β‐Mimicking Peptides as Tools To Study the CK2α/CK2β Interaction in Cancer Cells
Author(s) -
Lindenblatt Dirk,
Horn Mareike,
Götz Claudia,
Niefind Karsten,
Neundorf Ines,
Pietsch Markus
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800786
Subject(s) - hela , peptide , cancer cell , cytotoxicity , chemistry , hek 293 cells , recombinant dna , kinase , casein kinase 2 , protein subunit , microbiology and biotechnology , biochemistry , in vitro , cancer , biology , protein kinase a , receptor , gene , genetics , mitogen activated protein kinase kinase
The ubiquitously expressed Ser/Thr kinase CK2 is a key regulator in a variety of key processes in normal and malignant cells. Due to its distinctive anti‐apoptotic and tumor‐driving properties, elevated levels of CK2 have frequently been found in tumors of different origin. In recent years, development of CK2 inhibitors has largely been focused on ATP‐competitive compounds; however, targeting the CK2α/CK2β interface has emerged as a further concept that might avoid selectivity issues. To address the CK2 subunit interaction site, we have synthesized halogenated CK2β‐mimicking cyclic peptides modified with the cell‐penetrating peptide sC18 to mediate cellular uptake. We investigated the binding of the resulting chimeric peptides to recombinant human CK2α using a recently developed fluorescence anisotropy assay. The iodinated peptide sC18‐I‐Pc was identified as a potent CK2α ligand ( K i =0.622 μ m ). It was internalized in cells to a high extent and exhibited significant cytotoxicity toward cancerous HeLa cells (IC 50 =37 μ m ) in contrast to non‐cancerous HEK‐293 cells. The attractive features and functionalities of sC18‐I‐Pc offer the opportunity for further improvement.