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Theses

Microarrays fonctionnels de gouttes : de la synthèse chimique combinatoire au criblage de molécules bioactives.

Abstract : Microarrays are orderly arrangement of chemical, biological or cellular entities. This research field is rapidly growing because of high expectations in fondamental and applied sciences. The microarray technology is supported by three main methods: surface chemistry for slides functionnalisation, accurate technologies for manufacturing, and detection. Among possible applications, studying enzymatic activity is of high interest as it allows for monitoring the behaviour of enzymes in parallel, in the presence of a variety of substrates or inhibitors. Proteases play a key role in all living organisms and are therapeutic targets of choice, which make them promising enzymological models for microarrays.
Fast creation of microarrays made of hundreds of separated microdroplets on surface of a few cm2 is achieved with the technology developed in our lab. Each droplet behaves as an individual microreactor. The aim is to use for the first time this technology for chemical synthesis and proteolysis monitoring. These two approaches are then to be combined in an original way to carry out a screening experiment.
These microdroplets arrays were applied successfully to chemical synthesis of a library of inhibitors as well as for the screening of fluorescent products. Enzymology on chip was performed with papaïn, a metalloprotease and HCV protease NS3, using three different kinds of fluorogenic substrates. Finally, a sequential method based on the library assembly by chemical synthesis on microarray, followed by NS3 assay on the same microarray was tried for the first tthe screening of NS3 inhibitors. Promising hits displaying were discovered.
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https://tel.archives-ouvertes.fr/tel-00174806
Contributor : Pascal Martinez <>
Submitted on : Tuesday, September 25, 2007 - 12:56:47 PM
Last modification on : Wednesday, November 4, 2020 - 3:17:55 PM
Long-term archiving on: : Monday, September 24, 2012 - 12:46:32 PM

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  • HAL Id : tel-00174806, version 1

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Laurent Mugherli. Microarrays fonctionnels de gouttes : de la synthèse chimique combinatoire au criblage de molécules bioactives.. Sciences du Vivant [q-bio]. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00174806⟩

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