Universität zu Köln

Lindenblatt, Dirk ORCID: 0000-0002-5561-1082, Horn, Mareike, Goetz, Claudia, Niefind, Karsten ORCID: 0000-0002-0183-6315, Neundorf, Ines ORCID: 0000-0001-6450-3991 and Pietsch, Markus (2019). Design of CK2 beta-Mimicking Peptides as Tools To Study the CK2 alpha/CK2 beta Interaction in Cancer Cells. ChemMedChem, 14 (8). S. 833 - 842. WEINHEIM: WILEY-V C H VERLAG GMBH. ISSN 1860-7187

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Abstract

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 CK2 alpha/CK2 beta interface has emerged as a further concept that might avoid selectivity issues. To address the CK2 subunit interaction site, we have synthesized halogenated CK2 beta-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 CK2 alpha using a recently developed fluorescence anisotropy assay. The iodinated peptide sC18-I-Pc was identified as a potent CK2 alpha ligand (K-i=0.622 mu m). It was internalized in cells to a high extent and exhibited significant cytotoxicity toward cancerous HeLa cells (IC50=37 mu m) in contrast to non-cancerous HEK-293 cells. The attractive features and functionalities of sC18-I-Pc offer the opportunity for further improvement.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lindenblatt, Dirk UNSPECIFIED orcid.org/0000-0002-5561-1082 UNSPECIFIED Horn, Mareike UNSPECIFIED UNSPECIFIED UNSPECIFIED Goetz, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Niefind, Karsten UNSPECIFIED orcid.org/0000-0002-0183-6315 UNSPECIFIED Neundorf, Ines UNSPECIFIED orcid.org/0000-0001-6450-3991 UNSPECIFIED Pietsch, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-150618
DOI:	10.1002/cmdc.201800786
Journal or Publication Title:	ChemMedChem
Volume:	14
Number:	8
Page Range:	S. 833 - 842
Date:	2019
Publisher:	WILEY-V C H VERLAG GMBH
Place of Publication:	WEINHEIM
ISSN:	1860-7187
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-KINASE CK2; SMALL-MOLECULE INHIBITORS; CASEIN KINASE-2; BETA-SUBUNIT; IN-VITRO; ALPHA; CIGB-300; PHOSPHORYLATION; APOPTOSIS; SEQUENCE Multiple languages Chemistry, Medicinal; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15061