Linked Life Data

8459830

Source:http://linkedlifedata.com/resource/pubmed/id/8459830

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-4-27
pubmed:abstractText
The major proteolytic activity of Trypanosoma cruzi is a cathepsin L-like cysteine protease expressed in all stages of the parasite. As an initial step in identifying possible functions of this enzyme in the life cycle of T. cruzi, and examining its potential as a target for rational drug design, two fluoromethyl ketone-derivatized cysteine protease inhibitors were studied for their effects on T. cruzi infection of mammalian cells. Both inhibitors are irreversible substrate analogues with high specificity for cysteine proteases and minimal toxicity to mammalian cells. While micromolar concentrations of inhibitors had some effect on replication of all parasite stages, the most dramatic arrest of parasite replication occurred at the transformation of trypomastigote to amastigote, and also from amastigote to trypomastigote. It is therefore proposed that the enzyme functions in intracellular protein degradation in some stages of T. cruzi, but also in remodeling of the parasite during transformation between stages. Concentrations of inhibitors necessary to interrupt the parasite life cycle had no observable toxicity to macrophages, fibroblasts or epithelial cells in culture. Differential susceptibility of T. cruzi versus host cysteine proteases to fluoromethyl ketone protease inhibitors suggests that inhibition of the T. cruzi cysteine protease is a potential lead for new chemotherapy of Chagas' disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi.
pubmed:affiliation
Palo Alto Medical Foundation, CA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't