<i>Trans</i>‐Platinum/Thiazole Complex Interferes with Sp1 Zinc‐Finger Protein

Chen, Siming; Xu, Dechen; Jiang, Huan; Zhang, Xi; Zhu, Pingping; Liu, Yangzhong

doi:10.1002/ange.201206596

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…It has been found that cisplatin could react with some ZFPs resulting in the release of zinc ions from ZFPs and the perturbations of protein structures and functions , . However, some other ZFPs demonstrated a much lower reactivity to cisplatin . To further understand the influence of the zinc binding motif in the reaction with cisplatin, and also to exclude the possibility of varying results occurring from different investigation conditions, we conducted a reaction of three types of ZFPs under identical reaction conditions and analyzed the reactions using several methods, including NMR, HPLC, ESI‐MS, and CD spectra.…”

Section: Resultsmentioning

confidence: 99%

“…While a number of ZFPs demonstrated high reactivity to cisplatin, the zinc finger protein Sp1 showed very low reactivity to cisplatin, although this reaction can be significantly promoted by tris‐(2‐carboxyethyl) phosphine (TCEP) through a cisplatin‐TCEP intermediate . On the other hand, a trans ‐platinum derivative [PtCl 2 (NH 3 )(thiazole)] possesses a much higher reactivity than cisplatin to Sp1.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Unlike the reaction with H1, the nonlabile ligands were found to be preserved in the reaction of trans-EE or trans-PtTz with the human copper chaperone Atox1 or the Zinc-Finger protein Sp1. 58,59 ■ CONCLUSIONS…”

Section: ■ Discussionmentioning

confidence: 99%

Reaction of Histone H1 with trans-Platinum Complexes and the Effect on DNA Platination

Cheng

Yuan

et al. 2019

Inorg. Chem.

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Transplatin is an inactive platinum drug; however, a number of analogues, such as trans-EE and trans-PtTz, demonstrate promising antitumor activity in vitro and in vivo. Although the ultimate target is nuclear DNA, increasing evidence indicate that proteins also play important roles in the display of antitumor activity. The linker histone H1 is situated by the portal between the unwrapped DNA and the nucleosome core. Our recent study revealed that H1 can readily react with cisplatin, and the adducts tend to form ternary complexes with DNA. In this work, we have investigated the reaction of histone H1 with two antitumor-active trans-oriented complexes, trans-EE and trans-PtTz, and the effect of H1 upon the platination of DNA. The results show that trans-platinum drugs are much more reactive than cisplatin toward H1. Interestingly, in addition to the expected bidentate adducts (by displacement of the two labile chlorido ligands), also a tridentate adduct can be formed by displacement of one nonlabile carrier ligand of trans-EE or trans-PtTz. The trans-Pt/H1 adducts can then react with DNA and generate protein–Pt–DNA ternary complexes. Additionally, platinum can be transferred from trans-Pt/H1 adducts to DNA, generating binary trans-Pt/DNA complexes. Such a transfer of the platinum agent to DNA was not observed in the reaction of cisplatin. Furthermore, the detailed investigation carried out on a model peptide indicates that H1 promotes the DNA platination by trans-EE, while it reduces that of trans-PtTz and cisplatin. These results suggest that H1 can play a key role in the DNA platination and modulate the efficacy of different platinum agents.

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“…However, serious side effects from Pt(II) drugs have limited their clinical use. Recently, platinum(IV) (Pt(IV)) complexes were designed by introducing two additional ligands to the axial positions, which decompose to the corresponding toxic Pt(II) drugs under photoirradiation or chemical reduction. − Apart from being drugs, Pt could be used as a CT imaging contrast agent due to its high X-ray absorption coefficient . Compared to organic drug molecules, the use of Pt-based CT imaging could self-track the fate of Pt-based anticancer drugs in vivo .…”

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confidence: 99%

Tailoring Platinum(IV) Amphiphiles for Self-Targeting All-in-One Assemblies as Precise Multimodal Theranostic Nanomedicine

Zhang

et al. 2018

ACS Nano

117

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Drug, targeting ligand, and imaging agent are the three essential components in a nanoparticle-based drug delivery system. However, tremendous batch-to-batch variation of composition and drug content typically accompany the current approaches of building these components together. Herein, we report the design of photoactivatable platinum(IV) (Pt(IV)) amphiphiles containing one or two hydrophilic lactose targeting ligands per hydrophobic Pt(IV) prodrug for an all-in-one precise nanomedicine. Self-assembly of these Pt(IV) amphiphiles results in either micelle or vesicle formation with a fixed Pt/targeting moiety ratio and a constantly high content of Pt. The micelles and vesicles are capable of hepatoma cell-targeting, fluorescence/Pt-based CT imaging and have shown effective anticancer efficacy under laser irradiation in vitro and in vivo. This photoactivatable, active self-targeting, and multimodal theranostic amphiphile strategy shows great potential in constructing precise nanomedicine.

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Trans‐Platinum/Thiazole Complex Interferes with Sp1 Zinc‐Finger Protein

Cited by 6 publications

References 41 publications

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

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

Reaction of Histone H1 with trans-Platinum Complexes and the Effect on DNA Platination

Tailoring Platinum(IV) Amphiphiles for Self-Targeting All-in-One Assemblies as Precise Multimodal Theranostic Nanomedicine

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