Bioorg Med Chem Lett. 2013 Dec 31. pii: S0960-894X(13)01411-X. doi: 10.1016/j.bmcl.2013.12.039. [Epub ahead of print]

Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase-dihydrofolate reductase

Sharma H¹, Landau MJ², Sullivan TJ³, Kumar VP¹, Dahlgren MK³, Jorgensen WL³, Anderson KS⁴.

 

The parasite Toxoplasma gondii can lead to toxoplasmosis in those who are immunocompromised. To combat the infection, the enzyme responsible for nucleotide synthesis thymidylate synthase-dihydrofolate reductase (TS-DHFR) is a suitable drug target. We have used virtual screening to determine novel allosteric inhibitors at the interface between the two TS domains. Selected compounds from virtual screening inhibited TS activity. Thus, these results show that allosteric inhibition by small drug-like molecules can occur in T. gondii TS-DHFR and pave the way for new and potent species-specific inhibitors.
Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Dihydrofolate reductase, Thymidylate synthase, Toxoplasma gondii, Virtual screening

PMID:

24440298

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