Abstract EN:

Optical imaging is a continuously developing field of bio-organic chemistry over the past decades. The understanding of the physical phenomena and of the structure/photophysical properties relationship has resulted in the establishment of new strategies for the fluorogenic detection of (bio)analytes in vivo. Many tools have been developed leading to both sensitive and inexpensive diagnosis systems aiming at increasing their performances. My Ph. D. Thesis has been focused on the synthesis of new chemical tools (both quenchers and fluorescent organic dyes) for the development of new fluorogenic probes (based on FRET and/or pro-fluorescence concept) for the detection of enzymes in biological media. We proceeded to the synthesis of unsymmetrical sulforhodamines leading to novel fluorescent organic dyes whose the usefulness has been proved through the preparation of a wide range of new activatable "smart" optical bioprobes. In addition, a panel of various bioconjugatable quenchers (including water-soluble analogues) has been synthesized. Several synthetic routes have been developed for the rapid and effective access to new protease-sensitive "activatable" FRET-based probes. Some of them have been successfully applied to cellular molecular imaging assays. The major result of these works is probably the developement of two synthetic strategies to access to original heterotrifunctional molecular platforms for the simultaneous detection of two distinct protease activities. We expect that these tools could be highly useful for the early detection of some diseases as prostate cancer for which actual diagnosis technics based on detection/quantification of a single biomarker often lead to many false positive results.