Abstract
Glycolysis is an important metabolic pathway for most organisms, including protozoan parasites. Many of these primitive eukaryotes have streamlined their metabolism, favoring glycolysis for generating ATP in the glucose-rich environments in which they reside. Therefore, the enzymes involved in hexose metabolism could prove to be attractive targets for therapeutic development. This hypothesis is supported by a number of chemical and genetic validation studies. Additionally, the peculiar biochemistry of many of the components, along with limited protein sequence identity emphasizes the likelihood of developing compounds that selectively inhibit the parasite enzymes. In this review, we examine the status of target validation at the genetic and/or chemical levels from the protozoan parasites. While the proteins from some species have been interrogated to the point that well-defined lead compounds have been identified with activities against both enzyme and parasite growth, progress in other systems has to date been limited.
Keywords: Drug targets, glycolysis, metabolism, protozoa, therapeutics.
Current Medicinal Chemistry
Title:Targeting Protozoan Parasite Metabolism: Glycolytic Enzymes in the Therapeutic Crosshairs
Volume: 21 Issue: 15
Author(s): M.T. Harris, W.G. Mitchell and J.C. Morris
Affiliation:
Keywords: Drug targets, glycolysis, metabolism, protozoa, therapeutics.
Abstract: Glycolysis is an important metabolic pathway for most organisms, including protozoan parasites. Many of these primitive eukaryotes have streamlined their metabolism, favoring glycolysis for generating ATP in the glucose-rich environments in which they reside. Therefore, the enzymes involved in hexose metabolism could prove to be attractive targets for therapeutic development. This hypothesis is supported by a number of chemical and genetic validation studies. Additionally, the peculiar biochemistry of many of the components, along with limited protein sequence identity emphasizes the likelihood of developing compounds that selectively inhibit the parasite enzymes. In this review, we examine the status of target validation at the genetic and/or chemical levels from the protozoan parasites. While the proteins from some species have been interrogated to the point that well-defined lead compounds have been identified with activities against both enzyme and parasite growth, progress in other systems has to date been limited.
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Harris M.T., Mitchell W.G. and Morris J.C., Targeting Protozoan Parasite Metabolism: Glycolytic Enzymes in the Therapeutic Crosshairs, Current Medicinal Chemistry 2014; 21 (15) . https://dx.doi.org/10.2174/09298673113206660286
DOI https://dx.doi.org/10.2174/09298673113206660286 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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