Alexander Haseloer1, Tamara Lützenburg2, Joss Pepe Strache1, Jörg Neudörfl3, Ines Neundorf2, Axel Klein1. 1. Universität zu Köln, Department für Chemie, Institut für Anorganische Chemie, Greinstraße 6, 50939, Köln, Germany. 2. Universität zu Köln, Department für Chemie, Institut für Biochemie, Zülpicher Strasse 47a, 50674, Köln, Germany. 3. Universität zu Köln, Department für Chemie, Institut für Organische Chemie, Greinstraße 4, 50939, Köln, Germany.
Abstract
Three chiral tridentate N^N^S coordinating pyridine-carbaldehyde (S)-N4-(α-methylbenzyl)thiosemicarbazones (HTSCmB) were synthesised along with lysine-modified derivatives. One of them was selected and covalently conjugated to the cell-penetrating peptide sC18 by solid-phase peptide synthesis. The HTSCmB model ligands, the HTSCLp derivatives and the peptide conjugate rapidly and quantitatively form very stable PtII chlorido complexes [Pt(TSC)Cl] when treated with K2 PtCl4 in solution. The Pt(CN) derivatives were obtained from one TSCmB model complex and the peptide conjugate complex through Cl- →CN- exchange. Ligands and complexes were characterised by NMR, IR spectroscopy, HR-ESI-MS and single-crystal XRD. Intriguingly, no decrease in cell viability was observed when testing the biological activity of the lysine-tagged HdpyTSCLp, its sC18 conjugate HdpyTSCL-sC18 or the PtCl and Pt(CN) conjugate complexes in three different cell lines. Thus, given the facile and effective preparation of such Pt-TSC-peptide conjugates, these systems might pave the way for future use in late-stage labelling with Pt radionuclides and application in nuclear medicine.
Three chiral tridentate N^N^S coordinating pyridine-carbaldehyde (S)-N4-(α-methylbenzyl)n class="Chemical">thiosemicarbazones (HTSCmB) were synthesised along with lysine-modified derivatives. One of them was selected and covalently conjugated to the cell-penetrating peptidesC18 by solid-phase peptide synthesis. The HTSCmB model ligands, the HTSCLp derivatives and the peptide conjugate rapidly and quantitatively form very stable PtII chlorido complexes [Pt(TSC)Cl] when treated with K2 PtCl4 in solution. The Pt(CN) derivatives were obtained from one TSCmB model complex and the peptide conjugate complex through Cl- →CN- exchange. Ligands and complexes were characterised by NMR, IR spectroscopy, HR-ESI-MS and single-crystal XRD. Intriguingly, no decrease in cell viability was observed when testing the biological activity of the lysine-tagged HdpyTSCLp, its sC18 conjugate HdpyTSCL-sC18 or the PtCl and Pt(CN) conjugate complexes in three different cell lines. Thus, given the facile and effective preparation of such Pt-TSC-peptide conjugates, these systems might pave the way for future use in late-stage labelling with Pt radionuclides and application in nuclear medicine.
Authors: Wolfgang Kaim; Akbey Dogan; Matthias Wanner; Axel Klein; Ioannis Tiritiris; Thomas Schleid; Derk J Stufkens; Theo L Snoeck; Eric J L McInnes; Jan Fiedler; Stanislav Zális Journal: Inorg Chem Date: 2002-08-12 Impact factor: 5.165
Authors: Linda S Jongbloed; Nicolas Vogt; Aaron Sandleben; Bas de Bruin; Axel Klein; Jarl Ivar van der Vlugt Journal: Eur J Inorg Chem Date: 2018-04-27 Impact factor: 2.524