Towards more efficient glutathione peroxidase mimics: substrate recognition and catalytic group assembly.
Glutathione peroxidase (GPX) is a well-known selenoenzyme that functions as an antioxidant and catalyzes the reduction of harmful peroxide by glutathione and protects cells against oxidative damage. Because many diseases are related to oxidative stress, GPX is an ancient foe of many diseases. Antioxidants are very useful for biological bodies, and considerable effort has been spent to find compounds that could imitate the properties of GPX. This paper reviews GPX mimics developed so far and describes a new, more effective strategy for fabricating them. Although many GPX mimics have been made, they possess serious disadvantages: low activity, low solubility in water, and, in some cases, toxicity. In order to overcome these drawbacks, we have proposed a new strategy of imitating GPX. First, a receptor with a substrate binding site is generated. Next, a catalytic group is incorporated into the receptor near the substrate binding site, allowing the catalytic group access to the functional group of the substrate. Finally, a highly efficient enzyme mimic is obtained. Using this strategy, we successfully fabricated GPX mimics that use antibodies, cyclodextrins, some enzymes and proteins as receptors and chemical modification to incorporate the catalytic group, selenocysteine (Sec). The general principle of combining a functional group involved in catalysis with a specific binding site for the substrate is an approach that could be applied to the generation of other efficient semisynthetic biocatalysts. We describe the antioxidant activities of these GPX mimics and the reasons of their being promising candidates for medicinal applications.
Luo
Gui-min
GM
Key Laboratory of Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130023, P. R. China. gmluo@mail.jlu.edu.cn
Ren
Xiao-jun
XJ
Liu
Jun-qiu
JQ
Mu
Ying
Y
Shen
Jia-cong
JC
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002478:Cells, Cultured; D005979:Glutathione Peroxidase / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D018716:Molecular Mimicry; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013379:Substrate Specificity
D020011:Protective Agents; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase