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@unpublished{Baumann:2018:10.1101/248740,
author = {Baumann, H and Matthews, H and Li, M and Hu, JJ and Willison, K and Baum, J},
doi = {10.1101/248740},
publisher = {BioRxiv},
title = {A high-throughput in vitro translation screen towards discovery of novel antimalarial protein translation inhibitors},
url = {http://dx.doi.org/10.1101/248740},
year = {2018}
}

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TY  - UNPB
AB  - Drugs that target protein synthesis are well-validated for use as antimicrobials, yet specific high throughput (HTP) methods to screen for those targeting malaria are lacking. Here, we have developed a cell free in vitro translation (IVT) assay for the human malaria parasite, Plasmodium falciparum, which reconstitutes the native parasite protein translation machinery. Combining clarified IVT lysate with a click beetle luciferase reporter gene fused to untranslated regions of Pf histidine-rich proteins (hrp)-2 and 3, the HTP IVT assay accurately reports protein translation in a 384-well plate format using a standard spectrofluorometer. We validate the assay as effective in detecting compounds targeting the ribosome, ribosome co-factors (elongation factor 2) and cytosolic tRNA synthetases as well as its ability to find translation inhibitors in a blind screen using a high-density assay format amenable for high throughput. This demonstrates an ability to reconstitute the breadth of the parasite eukaryotic protein translation machinery in vitro and use it as a powerful platform for antimalarial drug discovery.
AU  - Baumann,H
AU  - Matthews,H
AU  - Li,M
AU  - Hu,JJ
AU  - Willison,K
AU  - Baum,J
DO  - 10.1101/248740
PB  - BioRxiv
PY  - 2018///
TI  - A high-throughput in vitro translation screen towards discovery of novel antimalarial protein translation inhibitors
UR  - http://dx.doi.org/10.1101/248740
UR  - http://hdl.handle.net/10044/1/68424
ER  -

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