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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Towards More Efficient Glutathione Peroxidase Mimics: Substrate Recognition and Catalytic Group Assembly

Author(s): Gui-min Luo, Xiao-jun Ren, Jun-qiu Liu, Ying Mu and Jia-cong Shen

Volume 10 , Issue 13 , 2003

Page: [1151 - 1183] Pages: 33

DOI: 10.2174/0929867033457502

Price: $65

Abstract

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.

Keywords: glutathione peroxidase, enzyme mimics, selenium, tellurium, molecular recognition, catalytic antibody, cyclodextrin, artificial imitation


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