报 告 人：ProfJens Hasserodt
工作单位：Université de Lyon-ENS de Lyon
报告时间：2015年5月5日（星期二）上午9:30-10:30
报告地点：生物楼5楼学术交流室
报告摘要:
Two lines of probes responding specifically to selected enzyme activity are presented. Targeting enzymes as biomarkers of life and disease takes advantage of increased detection sensitivity by catalytic (enzymatic) signal amplification, provided that probes are designed which act as true substrates and demonstrate multiple turnover. Off-on enzyme-responsive probes generate the signal from zero background, i.e. the imaging probes are invisible prior to encounter of the target enzyme (stealth probes), thus ensuring maximum detection sensitivity and allowing easier image interpretation. We proposed a general, highly modular 3-component probe design for peptidases[1] where the probe releases a phenolic fluorophore of one's choice for fluorescence imaging. The design's usefulness is demonstrated at the example of an invisible probe (off) targeting intracellular aminopeptidase activity and releasing a solid-state, ESIPT-type fluorophore which precipitates as highly fluorescent (on), photostable crystals in the cytoplasm.[2] This past
octobre, we reported a new probe technology called “Double Gating” that promises to offer significantly higher tissue specificity than habitual enzyme-responsive probes in future animal imaging. Secondly, we have introduced the first line of truly magnetogenic probes.[4,5] The probes are diamagnetic (invisible, off) and robust under physiological conditions and become paramagnetic (on) after irreversible transformation by the target analyte, either a chemical reactant or an enzyme. These probes have the potential for application to thein vitrodetection of paramagnetism in a biological fluid, or thein vivodetection by MRI.References:
[1]Thorn-Seshold O, Vargas-Sanchez M, McKeon S, Hasserodt J, ”A robust, high-sensitivity stealth probe for peptidases”Chem. Commun.2012,48,6253-6255
[2]Prost M, Canaple L, Samarut J, Hasserodt J, “Tagging live cells which express specific peptidase activity with solid-state fluorescence”ChemBioChem2014,15, 1413-1417.
[3]Prost M, Hasserodt, J, “Double Gating – a concept for enzyme-responsive imaging probes aiming at high tissue specificity”Chem. Comm.2014, DOI: 10.1039/C4CC07147F
[4]Hasserodt J, Kolanowski JL, Touti F. “Magnetogenesis in Water Induced by a Chemical Analyte”Angew. Chem. Int. Ed.2014, 53, 60-73.
[5]Touti F, Maurin P, Hasserodt J. “Magnetogenesis under physiological conditions with probes that report on (bio)chemical stimuli”Angew. Chem. Int. Ed.2013,52, 4654-8.
报告人简介：
Dr. Jens HASSERODT is Full Professor of Chemistry 1ere Classe at the University of Lyon-- Ecole Normale Supérieure de Lyon, France. He received his PhD from Heidelberg University in Germany in 1993.During1994-1996, he was postdoctoral research associate in The Scripps Research Institute, USA; During1996-1998, he wasstaff member in The Scripps Research Institute. During1998-2001, he was appointed as an Assistant Professor at The Scripps Research Institute. He has been a Professor in Ecole Normale Supérieure de Lyon since 2001. He was an Invited Professor at the University of Southern Calfornia in2014-15. His research interests have been directed towards the characterization of enzyme activity in vitro and in vivo. He has published 50 journal papers inAngew. Chem. Int. Ed., JACS, Journal of Medicinal Chemistry, Journal of Organic Chemistry,andChemical Communications. He has 8 patents, two of them licensed to a diagnostics company. He has received the CLARA Trophy for Innovation in 2009, and has been certified as “top reviewer” forAngew. Chem. Int. Ed.during the past 5 years (60 out of 5000 referees).
