title: Design of potent inhibitors for Schistosoma japonica glutathione S-transferase.
abstract: We implemented both structure-based drug design and the concept of polyvalency to discover a series of potent and unsymmetrical Schistosoma japonicum glutathione S-transferase (SjGST) inhibitors 10-12. This strategy achieved not only an excellent enhancement (10- to 490-fold) in the inhibitory potency, compared to the monofunctional analogues 1-5, but was also an effective modification by selecting a hydrophobic moiety with a flexible linker. The designed compounds with a low micromolar hit demonstrate special values in refining the new generation of SjGST inhibitors. The stoichiometry of the binding is one inhibitor molecule per SjGST monomer via isothermal titration calorimetric measurement.
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Jao
authors.forename: Jessica
authors.initials: J
authors.lastname: Chen
authors.forename: Kelvin
authors.initials: K
authors.lastname: Yang
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012547:Schistosoma / Q000201:enzymology*; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D017931:DNA Primers; D004791:Enzyme Inhibitors; D005982:Glutathione Transferase