McMillan P J, Patzewitz E M, Young S E, Westrop G D, Coombs G H, Engman L, Müller S
Division of Infection and Immunity and Wellcome Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, 120 University Place, University of Glasgow, Glasgow G12 8TA, UK.
Parasitology. 2009 Jan;136(1):27-33. doi: 10.1017/S0031182008005131. Epub 2008 Nov 4.
Thioredoxin reductase (TrxR), a NADPH-dependent disulfide oxidoreductase, is vital in numerous cellular processes including defence against reactive oxygen species, cell proliferation and signal transduction. TrxRs occur in 2 forms, a high Mr enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low Mr form is present in bacteria, fungi, plants and some protozoan parasites. Our hypothesis is that the differences between the forms can be exploited in the development of selective inhibitors. In this study, cyclodextrin- and sulfonic acid-derived organotelluriums known to inhibit mammalian TrxR were investigated for their relative efficacy against P. falciparum TrxR (PfTrxR), a high Mr enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low Mr form of TrxR. The results suggest that selective inhibition of low Mr TrxRs is a feasible goal.
硫氧还蛋白还原酶（TrxR）是一种依赖烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的二硫键氧化还原酶，在众多细胞过程中至关重要，包括抵御活性氧、细胞增殖和信号转导。TrxR有两种形式，一种是高分子量（Mr）的酶，以哺乳动物、疟原虫恶性疟原虫和一些蠕虫的TrxR为代表；另一种低Mr形式存在于细菌、真菌、植物和一些原生动物寄生虫中。我们的假设是，这些形式之间的差异可用于开发选择性抑制剂。在本研究中，研究了已知可抑制哺乳动物TrxR的环糊精和磺酸衍生的有机碲化合物对高分子量酶恶性疟原虫TrxR（PfTrxR）和低Mr形式的阴道毛滴虫TrxR（TvTrxR）的相对抑制效果。结果表明，选择性抑制低Mr的TrxR是一个可行的目标。
