Cisplatin Preferentially Binds to Zinc Finger Proteins Containing C3H1 or C4 Motifs

Abstract

Cisplatin is a widely used anticancer drug for the treatment of a variety of human malignancies. It has been reported that cisplatin could react with a variety of zinc finger proteins (ZFPs), which results in structural perturbation followed by malfunction of the proteins. However, some other ZFPs were found to be unreactive to cisplatin. The difference in the reactivity of various ZFPs remains unclear. Here we investigated the reaction of cisplatin with ZFPs containing different zinc binding motifs (C2H2, C3H, and C4). The zinc release assay and NMR spectroscopy revealed that both C3H and C4 types of ZFPs are highly reactive to cisplatin, whereas the C2H2 type of

Selective Targeting of the Zinc Finger Domain of HIV Nucleocapsid Protein NCp7 with Ruthenium Complexes

“…It has been reported that Ru compounds exhibited different reactivity to DNA or proteins; particularly, the selectivity of Ru‐agents varies dependent upon the target of biomolecules . The different types of zinc finger proteins, such as CCHH, CCHC, and CCCC domains, are known to have different reactivity to metallodrugs . In addition, the protein sequence and residues around zinc center also influence the reactivity of the protein.…”

“…[23b] The different types of zinc finger proteins,s uch as CCHH, CCHC, and CCCC domains, are known to have different reactivity to metallodrugs. [7,28] In addition, the protein sequence and residues aroundz inc center also influencet he reactivity of the protein. For instance, the pstacking between aromatic residues of proteins and ligand of metal complexesc an enhance their reactions.…”

A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells

“…18 It has been reported that the binding of many metallodrugs, such as arsenic, platinum, and ruthenium agents, to zinc-nger proteins induces the release of zinc ions from the proteins. [18][19][20] Here we observed that the reaction of Ru-1 also resulted in zinc release from PML (Fig. 4B).…”

Role of CCCH-Type Zinc Finger Proteins in Human Adenovirus Infections

“…Truly, zinc ion replacement with gold, platinum, cobalt, and selenium complexes can disrupt ZnF protein binding to nucleic acids [ 90 ]. Further, cisplatin, a well-known platinum-based anti-cancer drug, can selectively bind to and cause structural perturbation of some ZnF motifs [ 91 ]. It remains to be tested whether any of the metal-based compounds can alter the biological functions of the ZC3H11A protein.…”