Research

Metal Chelator-Based Chemotherapeutic Agents for Alzheimer's Disease (AD) | Metallopeptides as Efficient and Selective Oxidation Catalysts | Metal-Based Reagents Toward Detoxification of H₂O₂ in Biological Systems

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Metal Chelator-Based Chemotherapeutic Agents for Alzheimer's Disease (AD)

A distinct feature of AD is accumulation of toxic amyloid-beta (Aβ) aggregates, which is accelerated by the presence of divalent ions such as Cu(II) and Zn(II) . In particular, Cu-Aβ may catalytically generate reactive oxygen species (ROS) leading to increased oxidative stress and consequent deterioration of AD conditions. Metal-induced Aβ aggregation and ROS formation can be alleviated by metal chelators. Therefore, we will develop a new generation of nontoxic, small molecule-based metal chelators for Cu(II) and Zn(II) as effective therapeutics for AD.

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Metallopeptides as Efficient and Selective Oxidation Catalysts

Selective oxidation reactions of organic compounds are of great significance for the synthesis of fine chemicals and industrial production of useful compounds. To achieve efficiency and selectivity, transition metal complexes and metalloenzymes have been employed as catalysts. Their utility and general applicability are still limited, however. We will design metallopeptides as a new class of catalysts for selective oxidative functionalization under mild conditions. Metallopeptide-based catalysts would combine advantages of both metalloenzymes and small-molecule catalysts that are involved in oxidation chemistry.

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Metal-Based Reagents Toward Detoxification of H₂O₂ in Biological Systems

Impaired detoxification of hydrogen peroxide (H₂O₂) and the resulting oxidative stress are implicated in human diseases including a number of forms of cancer. In cellular antioxidant defense systems, catalase acts as an enzymatic scavenger of H₂O₂, converting it to dioxygen and water. Inspired by the structure and function of this enzyme, we will construct an efficient detoxifier of H₂O₂ in biological systems.

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