title: Trypanocidal activity of peptidyl vinyl ester derivatives selective for inhibition of mammalian proteasome trypsin-like activity.
abstract: Nine vinyl ester tripeptides selective for inhibition of mammalian proteasome trypsin-like activity were tested for in vitro activity against Trypanosoma brucei. Interestingly, two compounds showed trypanocidal activity in the low micromolar range without displaying cytotoxicity against human cells. However, the compounds did not inhibit the trypsin-like activity of the trypanosome proteasome although their effect correlates with inactivation of the chymotrypsin-like activity. This finding shows that the inhibitor sensitivities between mammalian and trypanosome proteasome are distinct. This difference may be exploited for rational anti-trypanosomal drug development.
authors: BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. dsteverding@hotmail.com
authors: Dietmar
authors: D
authors: Steverding
authors: Anna
authors: A
authors: Baldisserotto
authors: Xia
authors: X
authors: Wang
authors: Mauro
authors: M
authors: Marastoni
mesh_terms: D004952:Esters; D018922:HL-60 Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D061988:Proteasome Inhibitors; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004952:Esters; D010455:Peptides; D061988:Proteasome Inhibitors; D014344:Trypanocidal Agents; D014361:Trypsin Inhibitors; D046988:Proteasome Endopeptidase Complex