Design, synthesis and evaluation of D-homophenylalanyl epoxysuccinate inhibitors of the trypanosomal cysteine protease cruzain

Authors
Roush, WR Hernandez, AA McKerrow, JH Selzer, PM Hansell, E Engel, JC
Citation
Wr. Roush et al., Design, synthesis and evaluation of D-homophenylalanyl epoxysuccinate inhibitors of the trypanosomal cysteine protease cruzain, TETRAHEDRON, 56(50), 2000, pp. 9747-9762
Citations number
73
Categorie Soggetti
Chemistry & Analysis","Organic Chemistry/Polymer Science
Journal title
TETRAHEDRON
ISSN journal
00404020 → ACNP
Volume
56
Issue
50
Year of publication
2000
Pages
9747 - 9762
Database
ISI
SICI code
0040-4020(200012)56:50<9747:DSAEOD>2.0.ZU;2-0
Abstract
The binding modes of E-64c to papain combined with molecular modeling and l igand design using the crystal structure of cruzain have been used to devel op new, potent D-Homophenylalanyl epoxysuccinate inhibitors of cruzain, the major cysteine protease of Trypanosoma cruzi. The most potent inhibitor 47 contains an O-benzyl hydroxamate unit and is highly specific for cruzain r elative to other cysteine proteases tested. (C) 2000 Elsevier Science Ltd. All rights reserved.