6533b85bfe1ef96bd12baa1f
RESEARCH PRODUCT
Targeting of the Leishmania Mexicana cysteine protease CPB2.8 ΔCTE by decorated fused benzo[b] thiophene scaffold.
Anna PipernoJ. KesselringAntonio RescifinaNicola MicaleTanja SchirmeisterAngela ScalaGiovanni Grassisubject
0301 basic medicinebiology010405 organic chemistryChemistryStereochemistryGeneral Chemical EngineeringActive siteGeneral ChemistryHighly selectivebiology.organism_classification01 natural sciencesCysteine proteaseLeishmania mexicana0104 chemical sciences03 medical and health scienceschemistry.chemical_compound030104 developmental biologyCovalent bondDocking (molecular)biology.proteinThiopheneDRUG DISCOVERY SOFTWARE NEWS FORCE-FIELD CATHEPSIN-L INHIBITORS OPTIMIZATION TRYPANOSOMIASIS IDENTIFICATION PROTEINASES VALIDATIONIC50description
A potent and highly selective anhydride-based inhibitor of Leishmania mexicana cysteine protease CPB2.8ΔCTE (IC50 = 3.7 μM) was identified. The details of the interaction of the ligand with the enzyme active site were investigated by NMR biomimetic experiments and docking studies. Results of inhibition assays, NMR and theoretical studies indicate that the ligand acts initially as a non-covalent inhibitor and later as an irreversible covalent inhibitor by chemoselective attack of CYS 25 thiolate to an anhydride carbonyl.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 |