Hoyer, Jan, Schatzschneider, Ulrich, Schulz-Siegmund, Michaela ORCID: 0000-0003-1340-1850 and Neundorf, Ines ORCID: 0000-0001-6450-3991 (2012). Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery. Beilstein J. Org. Chem., 8. S. 1788 - 1798. FRANKFURT AM MAIN: BEILSTEIN-INSTITUT. ISSN 1860-5397

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Over the past 20 years, cell-penetrating peptides (CPPs) have gained tremendous interest due to their ability to deliver a variety of therapeutically active molecules that would otherwise be unable to cross the cellular membrane due to their size or hydrophilicity. Recently, we reported on the identification of a novel CPP, sC18, which is derived from the C-terminus of the 18 kDa cationic antimicrobial protein. Furthermore, we demonstrated successful application of sC18 for the delivery of functionalized cyclopentadienyl manganese tricarbonyl (cymantrene) complexes to tumor cell lines, inducing high cellular toxicity. In order to increase the potential of the organometallic complexes to kill tumor cells, we were looking for a way to enhance cellular uptake. Therefore, we designed a branched dimeric variant of sC18, (sC18)(2), which was shown to have a dramatically improved capacity to internalize into various cell lines, even primary cells, using flow cytometry and fluorescence microscopy. Cell viability assays indicated increased cytotoxicity of the dimer presumably caused by membrane leakage; however, this effect turned out to be dependent on the specific cell type. Finally, we could show that conjugation of a functionalized cymantrene with (sC18)(2) leads to significant reduction of its IC50 value in tumor cells compared to the respective sC18 conjugate, proving that dimerization is a useful method to increase the drug-delivery potential of a cell-penetrating peptide.

Item Type: Journal Article
CreatorsEmailORCIDORCID Put Code
Schulz-Siegmund, MichaelaUNSPECIFIEDorcid.org/0000-0003-1340-1850UNSPECIFIED
Neundorf, InesUNSPECIFIEDorcid.org/0000-0001-6450-3991UNSPECIFIED
URN: urn:nbn:de:hbz:38-480947
DOI: 10.3762/bjoc.8.204
Journal or Publication Title: Beilstein J. Org. Chem.
Volume: 8
Page Range: S. 1788 - 1798
Date: 2012
Place of Publication: FRANKFURT AM MAIN
ISSN: 1860-5397
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
Chemistry, OrganicMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48094


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