Goldi III Complexes Designed for Selective Targeting and Inhibition of Zinc

Zinc is an essential trace element that plays a critical role in various biological processes, including enzymatic activity, gene expression, and signal transduction. While zinc is vital for overall health, excessive zinc accumulation can lead to various diseases such as cancer, Alzheimer's, and Parkinson's. Developing strategies for selectively targeting and inhibiting zinc is of great interest in the field of medicinal chemistry.

In recent years, gold complexes have emerged as promising candidates for targeting and inhibiting zinc due to their unique chemical properties. Specifically, Gold(I) and Gold(III) complexes have shown remarkable potential in selectively binding to and modulating the activity of zinc ions.

The Role of Zinc in Biological Systems

Zinc is involved in a multitude of biological functions, and its homeostasis is tightly regulated by various zinc transporters and metallothioneins. It serves as a structural component in numerous proteins and enzymes, influencing their stability and catalytic activity. Zinc is also implicated in DNA binding, cell signaling, and immune response.

Gold(I,III) Complexes Designed for Selective Targeting and Inhibition of Zinc Finger Proteins (Springer Theses)

by Klaus J. Puettmann(1st ed. 2018 Edition)

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However, abnormalities in zinc levels can disrupt cellular processes and lead to pathological conditions. For instance, zinc dysregulation has been linked to the formation of beta-amyloid plaques in Alzheimer's disease. Zinc-dependent enzymes also play a role in cancer progression and metastasis.

Gold Complexes as Selective Zinc Inhibitors

Gold complexes, particularly Gold(I) and Gold(III) complexes, have shown promising results in selectively targeting and inhibiting zinc. These complexes possess a high affinity for zinc ions, allowing them to bind specifically to zinc-binding sites in proteins. This targeted binding inhibits the activity of zinc-dependent enzymes and disrupts zinc-mediated signaling pathways.

One of the main advantages of using gold complexes is their ability to selectively target zinc without interfering with other metal ions in the body. This selectivity is crucial for minimizing off-target effects and reducing toxicity.

Designing Gold(III) Complexes for Zinc Inhibition

Gold(III) complexes, in particular, have garnered significant attention due to their unique properties and reactivity. These complexes typically feature a gold center coordinated with ligands that facilitate zinc binding and inhibition. The ligand design plays a crucial role in determining the specificity and potency of the gold complex.

Researchers have developed a range of Gold(III) complexes with different ligand architectures and characteristics. These complexes can be tailored to target specific zinc-binding proteins or enzymes, allowing for personalized inhibition strategies.

Example 1: Gold(III)-Thiosemicarbazone Complexes

Thiosemicarbazone ligands have been widely used in the design of gold complexes for selective zinc inhibition. These ligands possess a sulfur and nitrogen donor set, facilitating coordination with gold and zinc ions. The resulting gold-thiosemicarbazone complexes can effectively target zinc-dependent proteins, such as matrix metalloproteinases (MMPs),which play a crucial role in cancer metastasis.

Studies have shown that gold-thiosemicarbazone complexes inhibit MMP activity by binding to the zinc catalytic site. This inhibition prevents MMP-mediated degradation of the extracellular matrix and reduces cancer cell invasion and migration.

Example 2: Gold(III)-Dithiocarbamates Complexes

Dithiocarbamates are another class of ligands commonly used in gold complex design. These ligands contain a carbonyl sulfur and nitrogen donor set, allowing for efficient coordination with gold and zinc ions. Gold-dithiocarbamate complexes have demonstrated potent inhibition of zinc finger proteins, which are involved in DNA binding and gene regulation.

By selectively targeting zinc finger proteins, gold-dithiocarbamate complexes can modulate gene expression and disrupt zinc-dependent signaling pathways. This targeted inhibition holds promise for developing therapeutic interventions for diseases driven by aberrant gene regulation.

Advancing Gold Complexes for Zinc Inhibition

The field of gold complexes designed for selective zinc inhibition is continuously evolving, with researchers exploring new ligand architectures and metal centers to enhance specificity and potency. By gaining a deeper understanding of the structural and chemical properties of gold complexes, scientists can further optimize their design and therapeutic potential.

Beyond inhibiting zinc, gold complexes also offer the benefits of metal-based anticancer agents. The unique properties of gold complexes, such as their ability to target specific proteins and enzymes involved in cancer progression, make them attractive candidates for targeted therapy.

Gold(III) complexes designed for selective targeting and inhibition of zinc have emerged as promising candidates in the field of medicinal chemistry. These complexes offer the potential to modulate zinc-dependent processes and disrupt zinc-mediated signaling pathways implicated in various diseases.

The ongoing research in this area aims to further optimize the design and therapeutic potential of gold complexes, paving the way for personalized and targeted interventions for diseases driven by zinc abnormalities.

As the understanding of the intricate interplay between zinc and biological systems continues to grow, gold complexes hold great promise for the development of innovative treatments. Through careful design and exploration of their properties, gold(III) complexes might become valuable tools in improving human health.

Gold(I,III) Complexes Designed for Selective Targeting and Inhibition of Zinc Finger Proteins (Springer Theses)

by Klaus J. Puettmann(1st ed. 2018 Edition)

4.6 out of 5

Language	:	English
File size	:	2020 KB
Text-to-Speech	:	Enabled
Screen Reader	:	Supported
Print length	:	208 pages

FREE

This book examines Au (I, III) complexes that selectively attack and inhibit zinc finger proteins (ZnFs) for potential therapeutic use. The author explores gold(I)-phosphine, gold(III) complexes with N^N and C^N donors as inhibitors of the HIV-1 nucleocapsid protein (NCp7),in comparison to the human transcription factor Sp1. To determine the coordination sphere of the gold adducts formed by interaction with ZnFs, two innovative approaches are used, based on Travelling-Wave Ion Mobility coupled with Mass Spectrometry (TWIM-MS),and X-ray Absorption Spectroscopy. Both approaches are proven to yield valuable structural information regarding the coordination sphere of gold in the adducts. In addition, the organometallic compound [Au (bnpy)Cl2] is evaluated. The system is shown to be capable of inhibiting ZnFs by means of C–S coupling.