Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form
D-Scholarship @ Pitt Banner and Links to Homepage

Post-translational import of protein into the endoplasmic reticulum of a trypanosome: An in vitro system for discovery of anti-trypanosomal chemical entities

Patham, B and Duffy, J and Lane, A and Davis, RC and Wipf, P and Fewell, SW and Brodsky, JL and Mensa-Wilmot, K (2009) Post-translational import of protein into the endoplasmic reticulum of a trypanosome: An in vitro system for discovery of anti-trypanosomal chemical entities. Biochemical Journal, 419 (2). 507 - 517. ISSN 0264-6021

[img] Plain Text (licence)
Available under License : See the attached license file.
Download (1kB)

Abstract

HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5 μM (MAL3-101), 3.3 μM (equisetin) and 7 μM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify 'new chemical entities' (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development. © The Authors Journal compilation.

Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Patham, B
Duffy, J
Lane, A
Davis, RC
Wipf, Ppwipf@pitt.eduPWIPF
Fewell, SW
Brodsky, JLjbrodsky@pitt.eduJBRODSKY0000-0002-6984-8486
Mensa-Wilmot, K
Date: 15 April 2009
Date Type: Publication
Journal or Publication Title: Biochemical Journal
Volume: 419
Number: 2
Page Range: 507 - 517
DOI or Unique Handle: 10.1042/bj20081787
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0264-6021
MeSH Headings: Animals; Endoplasmic Reticulum--metabolism; HeLa Cells; Humans; Naphthalenes--pharmacology; Protein Transport--drug effects; Pyrrolidinones--pharmacology; Rats; Tetrahydronaphthalenes--pharmacology; Trypanosoma brucei brucei--metabolism; Variant Surface Glycoproteins, Trypanosoma--genetics; Variant Surface Glycoproteins, Trypanosoma--metabolism
Other ID: NLM NIHMS140541, NLM PMC2769561
PubMed Central ID: PMC2769561
PubMed ID: 19196237
Date Deposited: 12 Jun 2013 20:29
Last Modified: 22 Jun 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/18942

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

Actions (login required)

View Item View Item