Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Chem Biol. 2008 Jan;15(1):70-7. doi: 10.1016/j.chembiol.2007.12.010.

Targeting a prokaryotic protein in a eukaryotic pathogen: identification of lead compounds against cryptosporidiosis.

Author information

  • 1Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA.

Erratum in

  • Chem Biol. 2008 Feb;15(2):200.

Abstract

Cryptosporidium 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.

PMID:
18215774
[PubMed - indexed for MEDLINE]
PMCID:
PMC2441818
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk