Eukaryotic Pathogens Innovation Center, 249 Life Sciences Building, 190 Collings Street, Clemson University, Clemson, SC 29634, USA.
Curr Med Chem. 2014;21(15):1668-78. doi: 10.2174/09298673113206660286.
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.
糖酵解是大多数生物包括原生动物寄生虫的重要代谢途径。这些原始真核生物简化了它们的新陈代谢，在富含葡萄糖的环境中有利于糖酵解来产生 ATP。因此，参与己糖代谢的酶可能成为治疗开发的有吸引力的靶点。这一假说得到了许多化学和遗传验证研究的支持。此外，许多成分的特殊生物化学特性以及有限的蛋白质序列同一性强调了开发选择性抑制寄生虫酶的化合物的可能性。在这篇综述中，我们从原生动物寄生虫的遗传和/或化学水平检查了靶标验证的现状。虽然已经对一些物种的蛋白质进行了研究，已经确定了具有针对酶和寄生虫生长活性的明确先导化合物，但迄今为止，其他系统的进展有限。
