Binding of RuCp complexes with human apo-transferrin: fluorescence spectroscopy and molecular docking methods

• Published in: Biometals Vol. 34; no. 5; pp. 1029 - 1042
• Main Authors: Santos, Filipa C., Costa, Paulo J., Garcia, M. Helena, Morais, Tânia S.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2021; Springer Nature B.V
• Subjects: Binding; Binding sites; Biochemistry; Biomedical and Life Sciences; Breast cancer; Cell Biology; Collision dynamics; Coordination compounds; Cytotoxic agents; Cytotoxicity; Estrogens; Fluorescence; Fluorescence spectroscopy; Hydrophobicity; Life Sciences; Medicine/Public Health; Microbiology; Molecular docking; Ovaries; Pharmacology/Toxicology; Plant Physiology; Plasma; Prostate; Proteins; Spectrum analysis; Toxicity; Transferrin; Tumor cell lines; Ruthenium (II); Fluorescence spectroscopy; Docking simulations; Metallodrugs; Human serum transferrin; Metal–protein interaction
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-021-00325-w

The interaction between human serum transferrin (hTf) and three promising organometallic Ru (II)- (η 5 -C 5 H 5 ) derived complexes, that have already shown strong in vitro cytotoxicity towards human cancer cell lines, has been investigated using fluorescence spectroscopic techniques. The results suggested that the formation of Ru-hTf systems involves a dynamic collision. The binding process occurs spontaneously (ΔG < 0), mainly driven by hydrophobic interactions. Additional docking studies show that all complexes bind preferably to a specific hydrophobic pocket in the C2-subdomain as already observed for other metal-cyclopentadienyl (MCp) complexes and are in agreement with the experimental results. With these studies we hope to contribute to the understanding of the mechanism of action of these promising cytotoxic agents, thus providing clues for a more rational design. Graphic abstract