6WX5

Adducts formed after 3 weeks in the reaction of chlorido[chlorido(2,2'-((2-([2,2':6',2''-Terpyridin]-4'-yloxy)ethyl)azanediyl)bis(ethan-1-ol))platinum(II)] with HEWL

Summary for 6WX5

• Entry DOI: 10.2210/pdb6wx5/pdb
• Descriptor: Lysozyme, SODIUM ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: metal-based, anticancer, platinum, terpyridine, lysozyme, metallodrug, hydrolase
• Biological source: Gallus gallus (Chicken)
• Total number of polymer chains: 1
• Total formula weight: 14608.27

Authors

Sullivan, M.P.,Hartinger, C.G.,Goldstone, D.C. (deposition date: 2020-05-09, release date: 2021-02-10, Last modification date: 2024-11-06)

Primary citation

Adams, M.,Sullivan, M.P.,Tong, K.K.H.,Goldstone, D.C.,Hanif, M.,Jamieson, S.M.F.,Hartinger, C.G.
Mustards-Derived Terpyridine-Platinum Complexes as Anticancer Agents: DNA Alkylation vs Coordination.
Inorg.Chem., 60:2414-2424, 2021

PubMed Abstract: The development of bifunctional platinum complexes with the ability to interact with DNA different binding modes is of interest in anticancer metallodrug research. Therefore, we report platinum(II) terpyridine complexes to target DNA by coordination and/or through a tethered alkylating moiety. The platinum complexes were evaluated for their antiproliferative properties against the human cancer cell lines HCT116 (colorectal), SW480 (colon), NCI-H460 (non-small cell lung), and SiHa (cervix) and generally exhibited potent antiproliferative activity although lower than their respective terpyridine ligands. H NMR spectroscopy and/or ESI-MS studies on the aqueous stability and reactivity with various small biomolecules, acting as protein and DNA model compounds, were used to establish potential modes of action for these complexes. These investigations indicated rapid binding of complex to the biomolecules through coordination to the Pt center, while in addition alkylated 9-ethylguanine. was investigated for its reactivity to the model protein hen egg white lysozyme (HEWL) by protein crystallography which allowed identification of the N atom of His15 as the binding site.

PubMed: 33497565
DOI: 10.1021/acs.inorgchem.0c03317

Experimental method

X-RAY DIFFRACTION (1.3 Å)