Presentation
The research group « Organic Chemistry for health and materials » from the UMR CNRS 6521 is composed by 26 persons including 13 permanent staff. The global skills of our group include both organic chemistry and coordination chemistry. In more details, we are working on organo-phosphorus chemistry, the synthesis and the coordination properties of polyazamacrocyclic compounds and the synthesis of amphiphilic compounds. Our research group is involved in numerus multidisciplinary research projects at the interface of biology and medicine (Imaging, therapy, radiopharmaceutics, nucleic acid delivery, ion channel modulation, bactericidal action) or for the development of new materials (bactericidal materials, multimeric materials & spin transition molecular materials). Our partners are academics and/or industrials. Our research group is built on two research axis: “Phosphorus, lipid & vectorization” and “azamacrocyclic compounds & coordination”.
Our web site : Team COSM’s website
Thematic
The permanent staff members included in this research axis have skills in organic synthesis, fluorescence measurements or in biology. Our research activity is focused on the synthesis of amphiphilic compounds, or phosphorus building blocks for the construction of hybrid materials. We also employed different physico-chemical characterizations to determine the size and charge of nanoobjects (DLS) or to study by fluorescent or by thermal technics (DSC) the dynamic of supramolecular packing. The molecules that are designed are used for different applications including nucleic acid delivery, the modulation of ion channels or for the preparation of hybrid materials. Most of these applications are developed jointly with different collaborations in France and abroad..
The use of nucleic acid for therapeutic purpose has demonstrated its efficacy. However the efficacy and the selectivity of the delivery remain a challenge. The use of nucleic acid for therapy can be applied to inherited (e.g. monogenic disease), acquired diseases (cancer) or to prevent diseases (e.g. vaccination). The efficacy of nucleic acid delivery (DNA, RNA, …) is still a challenge that require the evaluation of new carriers and new concepts. The carriers must be efficient but must also present a low cytotoxicity. Another important challenge is the need of synthesis protocols that can ideally be achieved following simple synthesis ptotocols and at a gram or multigram scale. In our group, we have reported the synthesis of bio-inspired cationic amphiphilic compounds that are efficient for nucleic acid delivery in vitro and in vivo. Of note the synthesis of these amphiphilic compounds is versatile thus permitting to modulate the structure and to evaluate the consequences on both the physico-chemical properties and transfection efficacies. This research topic is achieved in collaboration with biologists (UMR INSERM 1078 Brest and UPR CNRS 4301 Orléans). The applications that are studied include the development of new therapeutics for inherited disease (e.g. cystic fibrosis), for acquired diseases (cancer, tendon healing) or for vaccination. More recently, we developed new bactericidal agents that are efficient on multi-resistant strains.
This research activity, dedicated to the design of nucleic acid carriers, supported the creation of a platform that offers technical solutions for nucleic acid delivery. This SynNanoVect platform (https://www.univ-brest.fr/synnanovect/ )is granted by the IBISA label and is certificated ISO 9001 since 2013.
Some ion channels are implied in cancer development. The development of compounds that can regulate their action constitutes a new therapeutic strategy. In this direction SK3 ion channel (a potassium channel of small conductance regulated by intracellular calcium) was identified as an important partner regulating the migration of cancer cells. In our group we synthesized amphiphilic compound that modulate the activity of SK3 ion channel. Ohmline, which is one of the most efficient compound identify so far, proved to inhibit efficiently SK3 channels that consequently reduced cell migration and prevent the occurrence of bone metastases in a metastatic breast cancer model (Murine model). Our current efforts focused on the synthesis of new modulators of ion channel and on the mechanism of action of this class of compounds. This work is achieved jointly with the University of Tours (N2C, INSRM UMR 1069 – Tours), by ANR and La ligue contre le cancer.
Crystalline hybrid materials are prepared by the assembly of an organic building unit and a metallic salt. The properties of these materials depend on the structure of organic molecules, the nature of the metallic species and the structure of the assembly. We are working on the conception of original and adapted organic precursors that possess one or several phosphonic acid function. These compounds are used to prepare hybrid materials that are studied for their thermal stability, fluorescence or magnetic properties. Our effort also focused on the design of non-centrosymmetric materials. The synthesis of the materials is achieved in collaboration with the University of CAEN (CRISMAT, UMR CNRS 6508) and with the University of Strasbourg (IPCMS, UMR CNRS 7504).
- Cationic amphiphilic compounds for nucleic acid delivery and bactericidal action
The use of nucleic acid for therapeutic purpose has demonstrated its efficacy. However the efficacy and the selectivity of the delivery remain a challenge. The use of nucleic acid for therapy can be applied to inherited (e.g. monogenic disease), acquired diseases (cancer) or to prevent diseases (e.g. vaccination). The efficacy of nucleic acid delivery (DNA, RNA, …) is still a challenge that require the evaluation of new carriers and new concepts. The carriers must be efficient but must also present a low cytotoxicity. Another important challenge is the need of synthesis protocols that can ideally be achieved following simple synthesis ptotocols and at a gram or multigram scale. In our group, we have reported the synthesis of bio-inspired cationic amphiphilic compounds that are efficient for nucleic acid delivery in vitro and in vivo. Of note the synthesis of these amphiphilic compounds is versatile thus permitting to modulate the structure and to evaluate the consequences on both the physico-chemical properties and transfection efficacies. This research topic is achieved in collaboration with biologists (UMR INSERM 1078 Brest and UPR CNRS 4301 Orléans). The applications that are studied include the development of new therapeutics for inherited disease (e.g. cystic fibrosis), for acquired diseases (cancer, tendon healing) or for vaccination. More recently, we developed new bactericidal agents that are efficient on multi-resistant strains.
This research activity, dedicated to the design of nucleic acid carriers, supported the creation of a platform that offers technical solutions for nucleic acid delivery. This SynNanoVect platform (https://www.univ-brest.fr/synnanovect/ )is granted by the IBISA label and is certificated ISO 9001 since 2013.- Amphiphilic compounds for a selective modulation of ion channels
Some ion channels are implied in cancer development. The development of compounds that can regulate their action constitutes a new therapeutic strategy. In this direction SK3 ion channel (a potassium channel of small conductance regulated by intracellular calcium) was identified as an important partner regulating the migration of cancer cells. In our group we synthesized amphiphilic compound that modulate the activity of SK3 ion channel. Ohmline, which is one of the most efficient compound identify so far, proved to inhibit efficiently SK3 channels that consequently reduced cell migration and prevent the occurrence of bone metastases in a metastatic breast cancer model (Murine model). Our current efforts focused on the synthesis of new modulators of ion channel and on the mechanism of action of this class of compounds. This work is achieved jointly with the University of Tours (N2C, INSRM UMR 1069 – Tours), by ANR and La ligue contre le cancer.- Phosphonic acids precursors of hydrid materials
Crystalline hybrid materials are prepared by the assembly of an organic building unit and a metallic salt. The properties of these materials depend on the structure of organic molecules, the nature of the metallic species and the structure of the assembly. We are working on the conception of original and adapted organic precursors that possess one or several phosphonic acid function. These compounds are used to prepare hybrid materials that are studied for their thermal stability, fluorescence or magnetic properties. Our effort also focused on the design of non-centrosymmetric materials. The synthesis of the materials is achieved in collaboration with the University of CAEN (CRISMAT, UMR CNRS 6508) and with the University of Strasbourg (IPCMS, UMR CNRS 7504).
This thematic axis involved a permanent staff with an expertise in organic synthesis, macrocyclic chemistry, coordination at the interface of health (biological studies). The thematic group "Nitrogen Macrocycles and Coordination" focuses its research activity on the implementation of nitrogen chelates for health and materials. The group's know-how, focused on organic synthesis and ligand complexation chemistry, covering closely related fields such as the development of macrocyclic synthesis methodologies (cyclization, regioselective or specific functionalization, stereoselectivity), metal cation and anions coordination chemistry (synthesis of complexes, study of thermodynamic stability and kinetic inertia), supramolecular chemistry and molecular materials (host-guest self-assembly). These works are carried out with our colleagues from the Universities of A Coruña, Lisbon, Florence, Debrecen, Strasbourg, Lyon... Most of the activity is focused on, through the establishment of national and international collaborative consortia, the development of new diagnostic and therapies technologies for cancers or other diseases as leukemia, Alzheimer... (CHU Nantes, University Hospital Brest, NIH Washington, Universities of Paris 13, Toulouse, Fribourg, Ulsan ...).
The molecular objects developed, as well as the physico-chemical techniques mastered on site are also valued through academic collaborations: spin crossover, nanomaterials, substrate activation, catalysis... (intern collaboration at UMR CNRS 6521 in Brest or the University of Rennes, University of Hull, Paris Universities...) but also industrial with a strong interaction with major international companies operating in the field of health: Guerbet (France) Fluidigm (Canada, Ontario) or NECSA (South Africa). Finally, the group is at the origin of the start-up EasyChelators (Brest) in charge of enhancing the research of the group at the industrial level.
The projects of the group include:
Examples of developed macrocycles and detection of Zn2+ by MRI
64Cu PET imaging and two photon absorption bioprobes
The projects of the group include:- Synthesis of macrocycles derived from tacn, cyclen, pyclen and cyclam
- Functionalization of macrocycles and / or their specific (poly) functionalization.
- LCoordination study of macrocycles with different substrates (cations or anions): (poly) phosphates, F-, Mn2+, Fe2+, Cu2+, Cu+, Zn2+ (and other transition metals), Pb2+, Bi3+, Zr4+, Y3+, In3+ and Ln3+: thermodynamics and kinetics.
- Biological studies involving complexes (in vitro and in vivo).
- Optical imaging (luminescence of Ln3+ complexes), nuclear medicine 18F, 64Cu, 67Cu, 89Zr, 90Y, 213 /212Pb-Bi and mass cytometry (all metals).
- Industrial developments of the compounds.
Examples of developed macrocycles and detection of Zn2+ by MRI
64Cu PET imaging and two photon absorption bioprobesTeam members
Research programs
Aza Macrocycles and Coordination.
- Detection of cations and anions of biological interest in a biological environment
-European Programme Project PTDC/QUI 2016-2019 : Pr Rita Delgado (Lisbon, Portugal)
- Complexation; Medical screening / Therapy / Theranostic
– ANR « SADAM » 2017-2021 « Search And Destroy with AzaMacrocycles »
– La Ligue contre le Cancer (x4): 1 Doctoral Fellowship + 3 CSIRGO programmes
– Cancéropole Grand Ouest « Emergence »
– Brittany Region (ARED financial support)
– 1 Maturation Contract with SATT Ouest Valorisation
– Networks : GDR “FrenchBic”, ‘AIM” and “GPOL”.
– Industrial contract with Guerbet (Aulnay-sous-Bois) and 1 CIFRE Fellowship
– Industrial contract with NECSA (Pretoria, South Africa)
– Industrial contract with Fluidigm (Canada, Ontario) « CYTOCHEL ».
– Industrial contract with Quéguiner Group Brest.
– Industrial contract with EasyChelators (start-up hébergée au laboratoire)
Phosphorus, Lipids & Vectorisation.
- Amphiphilic compounds : Funded by AFM, VLM, La ligue contre le Cancer, maturation contract with SATT Ouest Valorisation. Member of the GDR phosphorus network, Biogenouest, Britany regional council, Cancéropôle Grand Ouest network, “Ion channel” network, ANR, Britany regional council, la ligue contre le cancer, research program with IFREMER Brest.
- Hybrid materials: ANR HYMN (2014-2018) ; GRD Phosphorus network.
Most significant Articles
- Amphiphilic compounds
- A. Le Moignic, V. Malard, T. Benvegnu, L. Lemiègre, M. Berchel, P-A. Jaffrès, C. Baillou, M. Delost, R. Macedo, J. Rochefort, G. Lescaille, C. Pichon, F.M. Lemoine, P. Midoux, V. Mateo Preclinical Evaluation of mRNA Trimannosylated Lipopolyplexes as Therapeutic Cancer Vaccines Targeting Dendritic Cells
J. Control. Release, 2018, 278, 110-121. - Afonso, D.; Le Gall, T.; Couthon-Gourvès, H.; Grélard, A.; Prakash, S.; Berchel, M.; Kervarec,N.; Dufourc,E.J.; Montier, T.; Jaffrès, P.A. Thiol-ene click reaction applied to cationic amphiphiles: impacts on supramolecular packing and gene transfection properties.
Soft Matter, 2016, 12, 4516 – 4520. - Loizeau, D. ; Jurkiewicz, P. ; Aydogan , G. ; Philimonenko , A. ; Mahfoudhi, S. ; Hozak , P. ; Maroto, A. ; Couthon-Gourvès, H. ; Jaffrès , P.A. ; Deschamps, L. ; Giamarchi, P. ; Hof , M. Biophysical properties of cationic lipophosphoramidates: vesicle morphology, bilayer hydration and lipid mobility
Colloids and Surfaces B: Biointerfaces, 2015, 136, 192-200 - P.A. Jaffrès, C. Gajate, A.M. Bouchet, H. Couthon-Gourvès, A. Chantôme, M. Potier-Cartereau, P. Besson, P. Bougnoux, F. Mollinedo, C. Vandier, Alkyl ether lipids and lipid raft reorganization in cancer therapy
Pharmacology & Therapeutics, 2016, 165, 114-131
- A. Le Moignic, V. Malard, T. Benvegnu, L. Lemiègre, M. Berchel, P-A. Jaffrès, C. Baillou, M. Delost, R. Macedo, J. Rochefort, G. Lescaille, C. Pichon, F.M. Lemoine, P. Midoux, V. Mateo Preclinical Evaluation of mRNA Trimannosylated Lipopolyplexes as Therapeutic Cancer Vaccines Targeting Dendritic Cells
- Macrocycles & Coordination
- Camus, Z. Halime, N. Le Bris, H. Bernard, C. Platas-Iglesias, R. Tripier. Full control of the regiospecific N-functionalization of new C‑functionalized cyclam bisaminal derivatives and application to the synthesis of their TETA, TE2A and CB-TE2A analogues. Org. Chem., 2014, 79, 1885−1899.
- Rodríguez-Rodríguez, Z. Halime, L. Lima, M. Beyler, D. Deniaud, N. Le Poul, R. Delgado, C. Platas-Iglesias, V. Patinec, R. Tripier, Cyclams with ambidentate methylthiazolyl pendants for a stable, inert and selective Cu(II)/Cu(I) coordination. Inorg. Chem., 2016, 55 (2), 619–632.
- Liu, A. Nonat, M. Beyler, M. Regueiro-Figueroa, K. Nchimi Nono, O. Jeannin, F. Camerel, F. Debaene, S. Cianférani-Sanglier, R. Tripier, C. Platas-Iglesias, L. J. Charbonnière. Supramolecular Luminescent Lanthanide Capsules for Fluoride Sequestering and Sensing Angew. Chem. Int. Ed, 2014, 53, 29, 7259-7263.
- A Rodríguez-Rodríguez, M. Regueiro-Figueroa, D. Esteban-Gómez, V. Patinec, R. Tripier, G. Tircsó, F. Carniato, M. Botta and C. Platas‑Iglesias, Modulating the Water Exchange Rate in Lanthanide(III) Complexes: the Labile Capping Bond Effect at Work. Chem. Eur. J., 2017, 23,5, 1110–1117
- Materials
- Q. Evrard, Z. Chaker, M. Roger, C. M. Sevrain, E. Delahaye, M. Gallart, P.Gilliot, C. Leuvrey, J.-M. Rueff, P. Rabu,C. Massobrio, M. Boero, A. Pautrat, P.-A.Jaffrès, G. Ori, G. Rogez Layered Simple Hydroxides Functionalized by Fluorene-Phosphonic Acids: Synthesis, Interface Theoretical Insights, and Magnetoelectric Effect.
Adv. Funct. Mater., 2017, 27, 1703576 - P. Burke, N. Baghdadi, A. E. Kownacka, S. Nigam, G. S. Clemente, M. M. Al-Yassiry, J. Domarkas, M. Lorch, M. Pickles, P. Gibbs, R. Tripier, C. Cawthorne, S J. Archibald, Facile gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions: evaluation as multimodal PET/MR liver imaging agents. Nanoscale, 2015, 7(36), 14889-14896.
- Q. Evrard, Z. Chaker, M. Roger, C. M. Sevrain, E. Delahaye, M. Gallart, P.Gilliot, C. Leuvrey, J.-M. Rueff, P. Rabu,C. Massobrio, M. Boero, A. Pautrat, P.-A.Jaffrès, G. Ori, G. Rogez Layered Simple Hydroxides Functionalized by Fluorene-Phosphonic Acids: Synthesis, Interface Theoretical Insights, and Magnetoelectric Effect.