Study of 8 Types of Glutathione Peroxidase Mimics Based on β-Cyclodextrin

Abstract

Glutathione peroxidase is key for the removal of H 2 O 2 and other hydroperoxides and therefore, it has an important role in the maintenance of the reactive oxygen species (ROS) metabolic balance in vivo. The native enzymes of the glutathione peroxidase family (GPx) have many defects, such as instability in vitro and poor availability. GPx mimetics has become a topic of considerable interest in artificial enzyme research. Many forms of GPx mimics have been synthesized, by including selenium and tellurium (double-bridged and single-bridged, 2-substituted and 6-substituted) in a mother molecule but differences the GPx mimics enzymatic activity have rarely been compared. We designed and synthesized eight cyclodextrin derivatives and used two types of enzyme assays to determine their activities. The results show that: (a) tellurium-containing GPx mimics have higher activity than that of selenium-containing GPx mimics; (b) dual-bridged mimics have higher activity than bis-bridged mimics; and (c) 2-position modified cyclodextrin has higher activity than 6-position modified cyclodextrin.

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

“…Moreover, the activity of dual-bridged enzymatic mimics was found to be higher than that of single-bridged ones. The relevance of these results goes beyond this isolated study: building a macromolecular structure around the artificial catalytic core paves the route to the development of mid-or high-molecular weight enzyme mimics which can selectively recognize substrates according to molecular shape, size, and non-covalent interactions within the cavity [152].…”

“…More recently, Vernekar and Mugesh studied the GPX-like mechanism of an ortho-alkylamino substituted diphenyl ditelluride [151]. High GPx-like activity has also been reported for a cyclodextrin-derived tellurium compound [152].…”

“…Li-Wu et al recently studied the use of Cyclodextrins (CDs) as host systems for the artificial catalytic core [152]. Cyclodextrins are cyclic oligosaccharides of at least six α-1-4-linked α-Dglucopyranoside units, with a peculiar internal toroidal shape with a cavity able to recognize and host several molecules.…”

Tocotrienol-Rich Fraction (TRF) Improves the Viability of Wild-Type Saccharomyces cerevisiae in the Initial Stationary Phase

“…Catalase and glutathione peroxidase are amongst the antioxidant enzymes to inactivate the ROS in cells. Catalase prevents cell damage by catalyzing the reduction of hydrogen peroxide to water and oxygen (Zeller & Klug 2004), while glutathione peroxidase catalyzes the reduction of hydrogen peroxide and other hydroperoxides to water or the corresponding alcohols, respectively, using glutathione as the reductant (Wang et al 2017). Hence, cells lacking antioxidant enzymes are expected to have shorter lifespan and slower reproduction (de Sá et al 2013;Demir & Koc 2010), as exhibited in Figure 1.…”

Biocatalysis and Biotransformations

“…Another important aspect which, in my opinion, additionally deserved research, concerns the application of methods other than protein engineering and immobilization, which could lead to more efficient biocatalysis. Two important examples are herein reported by Wang and coworkers, who designed and synthesized cyclodextrin derivatives which could serve as stable glutathione peroxidase mimics for the removal of H 2 O 2 and other hydroperoxides [33]. Similarly, Huang and coworkers design selenium-containing trypsin mimics that increase the substrate binding capacity and stability of glutathione peroxidases [34].…”