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Accueil > Animation scientifique & Evénements > Conférences CICB-Paris > Archives des conférences CICB-Paris de 2015

Bio-orthogonal and bio-specific bond-forming reactions for manipulation of biomolecules

par Marie Körner - publié le , mis à jour le

par Alain Wagner

Laboratory of Functional ChemoSystems, Labex MEDALIS - UMR 7199,
Faculty of Pharmacy, Illkirch Graffenstaden

La conférence aura lieu dans la salle R229 le jeudi 21 mai à 11 heures.

Résumé de la conférence

The efficient and selective cleavage of a chemical bond in response to the production by a living organism of a chemical mediator is the operative basis of many long-acting medicines, prodrugs or probes for imaging and diagnostic tests.
However, despite the recent outburst of biological chemistry that has stimulated the transversal approaches for the development of new bio-specific and/or bio-orthogonal chemical reactions, there has been only little attention on revisiting chemical bond breakage in complex biological media or even in living organisms.
Taking advantage of modern imaging methods we have developed an original chemometric methodology to figure the bio-responsivity profile of potentially labile chemical bond.
This led to the detection of particular bonds which cleavage is initiated by abnormal concentration of pathologically relevant chemical mediators (of thiols, ROS, NO, pH alteration). The bio-responsive functions exhibiting best selectivity, high reactivity, low toxicity and good metabolic stability, were utilized as switch to design new FRET based fluorescent probes. The turn-on probes were employed to monitor chemical bond cleavage and mediators miss regulation (over- or under-produced) in various representative cell and animal models.
By applying this methodology, we were able to characterize novel functional groups that exhibit a clean activation profile but also to uncover unexpected bio-reactivity. We will focus this presentation on recent results obtained on functional groups that undergo cleavage in response to biothiols or acidity miss regulation.

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