Institut de Chimie Moléculaire et des Matériaux d'Orsay

Laboratoire de Chimie Bioorganique et Bioinorganique - LCBB


Raphaël Labruère

Maître de Conférences

Institut de Chimie Moléculaire et des Matériaux d’Orsay
Université Paris-Sud, Bât 420
91405 Orsay Cedex

Tel : 01 69 15 36 94
Fax : 01 69 15 72 81

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Domaines de recherche : Thème 1

Development of small-molecule therapeutics and self-immolative spacers constructs as new tools in quantitative biology. Current research focuses on the development of both stimuli-responsive biological effectors containing a self-immolative spacer and anti infective agents.

Synthesis and biological evaluation of prodrugs activated by reactive oxygen species from the tumor environment
Cancer is one of the leading cause of death worldwide, accounting for 15 million deaths per year. The drugs available in clinic often present similar toxicity towards both cancer and normal cells. Therefore, there is an urgent requirement for alternative chemotherapies. A relevant strategy relies on the development of prodrugs, masked forms of active drugs that are designed to be activated after an enzymatic or a chemical reaction. In this project, prodrugs are prepared for the specific activation by the tumor environment. A targeting moiety is added to the prodrugs in order to increase the molecular uptake into cancer cells.
This project is currently funded by the “Ligue Nationale contre le Cancer”.
Postdoc (2016-present): Silvia Serra

Ecodesign of Drugs contaIning a selF-Immolative Scaffold (EDIFIS)
For many years, drugs and their metabolites have been subject to unrestricted emissions to the environment. The detection of an increasing number of pharmaceuticals in drinking water, coupled with their persistence in the environment, led to consider the environmental impact of a drug’s entire life cycle. In this context, the EDIFIS project focus on the development of a methodology for the ecodesign of drugs. The principle of our strategy is based on the programmed inactivation of drugs. Once entered the environment as waste, “ecodrugs” will undergo particular modification in the biomass, which will trigger the self-disassembly of the latter with loss of original activity. In our strategy, the sensitive moiety is a self-immolative scaffold as self-immolation processes are particularly well-studied. The drugs containing the latter scaffold will be deactivated by predictable metabolism either by hydrolytic or oxidative processes. Since 75% of the APIs on the market are not biodegradable, the first objective of this project is to redesign the most problematic drugs. The self-immolative moiety must be located within the molecule in such manner that the overall physicochemical, steric and complementary properties of the “ecodrugs” are very close to the lead compound.
This project relies on a national collaboration for the environmental fate of the new “ecodrugs” (Dr. Sylvie Nélieu, Ecosys, INRA/AgroParisTech) and is currently funded by the “Agence Nationale de la Recherche”.

Structure-guided design of pan inhibitors of metallo-β-lactamases (with Pr. L. Salmon and Dr. S. Pethe)
Identification of new pan-inhibitors of metallo-β-lactamases using a consensus pharmacophore common to all clinically-relevant metallo-β-lactamases.
This project is coordinated by Thierry NAAS (University Paris Sud, France) and funded by “Joint Programming Initiative on Antimicrobial Resistance”.
Partners: Youri Glupczynski, CHU Dinant Godinne UCL, Belgium ; Bogdan Iorga, Centre National de la Recherche Scientifique, ICSN, France ; Mariusz Jaskolski, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poland
Postdoc (2016-present): Alba Diez-Martinez

Enseignements :

Master de chimie M1
Bioconversions (cours/TD)

L2 DEUST Biotechnologies
Chimie organique (cours/TD)

Publications (2006-2018) :

A chemically-encoded timer for dual molecular delivery at tailored ranges and concentrations.
Silvia SERRA, Ahmed ALOUANE, Thomas LE SAUX, Steve HUVELLE, Raphaël PLASSON, Frédéric SCHMIDT, Ludovic JULLIEN, Raphaël LABRUERE
Chem. Commun. 2018, in press

Synthesis and antikinetoplastid evaluation of bis(benzyl)spermidine derivatives.
Elodie JAGU, Sébastien POMEL, Alba DIEZ-MARTINEZ, Estelle RASCOL, Stéphanie PETHE, Philippe M. LOISEAU, Raphaël LABRUERE
Eur. J. Med. Chem. 2018, 150, 655-666.

Polyamine-based analogs and conjugates as antikinetoplastid agents.
Elodie JAGU, Sébastien POMEL, Stéphanie PETHE, Philippe M. LOISEAU, Raphaël LABRUERE
Eur. J. Med. Chem. 2017, 139, 982-1015.

Synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates.
Elodie JAGU, Sébastien POMEL, Alba DIEZ-MARTINEZ, Florence RAMIANDRASOA , R. Luise KRAUTH-SIEGEL, Stéphanie PETHE, Casimir BLONSKI, Raphaël LABRUERE, Philippe M. LOISEAU
Bioorg. Med. Chem. 2017, 25, 84-90.

Water soluble 4-azapodophyllotoxin analogs.
Patent n°: WO 2015/107 119 A1 – Date of patent: Jul. 23, 2015

Self-Immolative Spacers: Kinetic Aspects, Structure–Property Relationships, and Applications.
Ahmed ALOUANE, Raphaël LABRUERE, Thomas LE SAUX, Frédéric SCHMIDT, Ludovic JULLIEN
Angew. Chem. Int. Ed. 2015, 54, 7492-7509.

Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives.
Elodie JAGU, Rachid DJILLALI, Sébastien POMEL, Florence RAMIANDRASOA, Stéphanie PETHE, Raphaël LABRUERE, Philippe M. LOISEAU, Casimir BLONSKI
Bioorg. Med. Chem. Lett. 2015, 25, 207-209.

Disassembly Kinetics of Quinone-Methide-Based Self-Immolative Spacers that Contain Aromatic Nitrogen Heterocycles.
Ahmed Alouane, Raphaël Labruère, Katherine J. Silvestre, Thomas Le Saux, Frédéric Schmidt, Ludovic Jullien
Chem Asian J. 2014, 9, 1334-1340.

Light-Activation for Versatile and Accurate Kinetic Analysis of Self-Immolative Spacers Disassembly.
Ahmed Alouane, Raphaël Labruère, Thomas Le Saux, Isabelle Aujard, Sylvie Dubruille, Frédéric Schmidt, Ludovic Jullien.
Chem. Eur. J. 2013, 19 (35), 11717–11724. Record of records. Chem. Rec. 2013, 13, 456–479.

New furo[3,4-b]quinolin-1(3H)-one scaffolds derived from γ-lactone fused quinolin-4(1H)-ones.
Raphaël Labruère, Philippe Helissey, Stéphanie Desbène-Finck, Sylviane Giorgi-Renault.
Helv. Chim. Acta. 2013, 96 (5), 919–923.

Thienopyrimidinedione formation versus ester hydrolysis from ureido carboxylic acid methyl ester.
Marie Reille-Seroussi,Raphaël Labruère, Nicolas Inguimbert, Sylvain Broussy, Nathalie Eilstein, Wang-qing Liu, Florent Huguenot, Michel Vidal.
Synthesis 2013, 45 (4), 479–490.

“Self-immolative” spacer for uncaging with fluorescence reporting.
Raphaël Labruère, Ahmed Alouane, Thomas Le Saux, Isabelle Aujard, Philippe Pelupessy, Arnaud Gautier, Sylvie Dubruille, Frédéric Schmidt, Ludovic Jullien.
Angew. Chem. Int. Ed. 2012, 124 (37), 9478–9481.

Attenuating the size and molecular carrier capabilities of polyacrylate nanoparticles by a hydrophobic fluorine effect.
Raphaël Labruère, Edward Turos.
Bioorg. Med. Chem.
2012, 20 (16), 5042–5045.

Synthesis of the 3,4,5-trimethoxy-2-(3,4-methylenedioxy-6-nitrophenyl)benzaldehyde for divergent preparation of cytotoxic biaryls.
Raphaël Labruère, Philippe Helissey, Stéphanie Desbène-Finck, Sylviane Giorgi-Renault.
Lett. Org. Chem. 2012, 9 (8), 568–571.

Poly(vinyl benzoate) nanoparticles for molecular delivery.
Edward Turos,Raphaël Labruère, Renaud Sicard, Ryan Cormier.
PCT Int. Appl. (2012), WO 2012068476.

Design, Synthesis and Biological Evaluation of the First Podophyllotoxin Analogues as Potential Vascular-Disrupting Agents.
Raphaël Labruère, Benoit Gautier, Marlène Testud, Christine Lenoir, Johanne Seguin, Stéphanie Desbène-Finck, Philippe Helissey, Guy G. Chabot, Christiane Garbay, Michel Vidal, Sylviane Giorgi-Renault.
ChemMedChem 2010, 5 (12), 2016–2025. Couverture intérieure de l’issue 12/2010. Cité en tant que “Hot article” et “the most accessed in 02/2011”

Poly(vinyl benzoate) nanoparticles for molecular delivery: Studies on their preparation and in vitro properties.
Raphaël Labruère, Renaud Sicard, Ryan Cormier, Edward Turos, Leigh West.
J. Control. Release 2010, 148 (2), 234–240.

Design and effective synthesis of the first 4-aza-2,3-didehydropodophyllotoxin rigid aminologue: a N-methyl-4-[(3,4,5-trimethoxyphenyl)amino)]-1,2-dihydroquinoline-lactone.
Raphaël Labruère, Stéphanie Desbène-Finck, Philippe Helissey, Sylviane Giorgi-Renault.
J. Org. Chem. 2008, 73 (9), 3642–3645.

Efficient syntheses of thiono and dithio analogues of tetronic acid.
Raphaël Labruère, Stéphanie Desbène-Finck, Philippe Helissey, Sylviane Giorgi-Renault.
Synthesis 2006, 24, 4163–4166.


Accueil LCBB