Cisplatin Preferentially Binds to Zinc Finger Proteins Containing C3H1 or C4 Motifs. Issue 12 (5th December 2016)

• Record Type: Journal Article
• Authors: Yuan, Siming; Ding, Xin; Cui, Yang; Wei, Kaiju; Zheng, Yuchuan; Liu, Yangzhong
• Other Names: Alessio Enzo guestEditor.; Guo Zijian guestEditor.
• Is Part Of: European journal of inorganic chemistry. Issue 12(2017)
• Page Start: 1778
• Page End: 1784
• Publication Date: 2016-12-05
• Subjects: Platinum -- Anticancer Drugs -- Zinc -- Proteins -- Circular dichroism; Chemistry, Inorganic -- Periodicals; Organometallic chemistry -- Periodicals; Bioinorganic chemistry -- Periodicals; Solid state chemistry -- Periodicals; 546
• DOI: 10.1002/ejic.201601140
• Languages: English
• ISSNs: 1434-1948

Abstract

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 ZFP is rather inert. The platination of the ZFPs caused the zinc ejection from the protein and disrupted the secondary structure. The time‐dependent HPLC measurement showed that the reaction of C3H and C4 types of ZFPs were also kinetically more favorable than the C2H2 type of ZFPs. ESI‐MS data confirmed the binding of up to three platinum atoms to the C3H and C4 ZFPs, whereas only a minor amount of monoplatinated C2H2 ZFP was formed. These results indicate that cisplatin preferentially binds to ZFPs containing C3H or C4 motifs, which could be correlated to the protein selectivity of cisplatin in the cellular environment. Abstract : Cisplatin selectively binds to ZFPs containing C4 or C3H motifs. MDM2‐zf (C4) and PARP‐1‐zf2 (C3H) show a higher reactivity to cisplatin than Sp1‐zf2 (C2H2). The platination of ZFPs causes the zinc release and structural perturbation of the proteins. The different reactivity of the various ZFPs may be correlated with the targeting of cisplatin in cells.