Please use this identifier to cite or link to this item:
Title: Incorporation of β-alanine in Cu(II) ATCUN peptide complexes increases ROS levels, DNA cleavage and antiproliferative activity
Author(s): Heinrich, Julian
Bossak-Ahmad, Karolina
Riisom, Mie
Haeri, Haleh H.
Steel, Tasha R.
Hergl, Vinja
Langhans, Alexander
Schattschneider, Corinna
Barrera, Jannis
Jamieson, Stephen M. F.
Stein, Matthias
Hinderberger, Dariush
Hartinger, Christian G.
Bal, Wojciech
Kulak, Nora
Issue Date: 2022
Type: Article
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-942581
Subjects: Redox-active Cu(II) complexes
Reactive oxygen species (ROS)
Human cancer
Abstract: Redox-active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades. High complex stability results in silencing of the Cu(II)/Cu(I) redox cycle and therefore leads to low ROS generation. In this work, we demonstrate that an exchange of the α-amino acid Gly with the β-amino acid β- Ala at position 2 (Gly2!β-Ala2) of the ATCUN motif reinstates ROS production (*OH and H2O2). Potentiometry, cyclic voltammetry, EPR spectroscopy and DFT simulations were utilized to explain the increased ROS generation of these β-Ala2- containing ATCUN complexes. We also observed enhanced oxidative cleavage activity towards plasmid DNA for β-Ala2 compared to the Gly2 complexes. Modifications with positively charged Lys residues increased the DNA affinity through electrostatic interactions as determined by UV/VIS, fluorescence, and CD spectroscopy, and consequently led to a further increase in nuclease activity. A similar trend was observed regarding the cytotoxic activity of the complexes against several human cancer cell lines where β-Ala2 peptide complexes had lower IC50 values compared to Gly2. The higher cytotoxicity could be attributed to an increased cellular uptake as determined by ICP-MS measurements.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Projekt DEAL 2021
Journal Title: Chemistry - a European journal
Publisher: Wiley-VCH
Publisher Place: Weinheim
Volume: 27
Issue: 72
Original Publication: 10.1002/chem.202102601
Page Start: 18093
Page End: 18102
Appears in Collections:Fakultät für Verfahrens- und Systemtechnik (OA)

Files in This Item:
File Description SizeFormat 
Heinrich et al._Incorporation of beta‐Alanine_2022.pdfZweitveröffentlichung2.58 MBAdobe PDFThumbnail