کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1392180 | 983718 | 2008 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Targeting a Prokaryotic Protein in a Eukaryotic Pathogen: Identification of Lead Compounds against Cryptosporidiosis Targeting a Prokaryotic Protein in a Eukaryotic Pathogen: Identification of Lead Compounds against Cryptosporidiosis](/preview/png/1392180.png)
SummaryCryptosporidium parvum is an important human pathogen and potential bioterrorism agent. No vaccines exist against C. parvum, the drugs currently approved to treat cryptosporidiosis are ineffective, and drug discovery is challenging because the parasite cannot be maintained continuously in cell culture. Mining the sequence of the C. parvum genome has revealed that the only route to guanine nucleotides is via inosine-5′-monophosphate dehydrogenase (IMPDH). Moreover, phylogenetic analysis suggests that the IMPDH gene was obtained from bacteria by lateral gene transfer. Here we exploit the unexpected evolutionary divergence of parasite and host enzymes by designing a high-throughput screen to target the most diverged portion of the IMPDH active site. We have identified four parasite-selective IMPDH inhibitors that display antiparasitic activity with greater potency than paromomycin, the current gold standard for anticryptosporidial activity.
Journal: - Volume 15, Issue 1, 25 January 2008, Pages 70–77