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

被引：10

作者：

Sharma, Hitesh ^{[1
]}

Landau, Mark J. ^{[1
,2
]}

Sullivan, Todd J. ^{[3
]}

Kumar, Vidya P. ^{[1
]}

Dahlgren, Markus K. ^{[3
]}

Jorgensen, William L. ^{[3
]}

Anderson, Karen S. ^{[1
,2
]}

机构：

[1] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA

[3] Yale Univ, Dept Chem, New Haven, CT 06520 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 04期

关键词：

Virtual screening; Thymidylate synthase; Dihydrofolate reductase; Toxoplasma gondii; ACTIVE SITE INHIBITOR; LIGAND-BINDING; CONFORMATION; STABILITY; PEPTIDES; INSIGHTS; DOCKING; SURFACE; TARGET; R163K;

D O I：

10.1016/j.bmcl.2013.12.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：1232 / 1235

页数：4