Chemical Library

Staff

Rodolphe Alves De Sousa

Rodolphe Alves De Sousa

Research Engineer

Phone: + 33 1 42 86 21 93
Email: 

Presentation chemical library

PRESENTATION

University of Paris Descartes and the Laboratory of Pharmaceutical and Toxicological Chemistry and Biochemistry (LCBPT) are associated to the “Chimiothèque Nationale” (CN) – French National Chemical Library of CNRS since 2004. Our laboratory is located at the chemistry / biology interface with various disciplinary activities. We develop both biologically active molecules for therapeutic purposes but also tools for the characterization of new targets, for the elucidation of biological mechanisms and for imaging. The teams are particularly distinguished in the development of probes and in various spectroscopic techniques such as EPR and NMR for in vitro and in vivo studies. The unit has expertise ranging from synthetic methodology to bioorganic and bioinorganic chemistry. Biological research themes focus mainly on anti-infectives (antibacterials, antivirals), anticancer drugs, the central nervous system, the immune system and toxicology.

Goals

We have established a pool of products of interest, which after verification of their purity, have been integrated into an electronic database common to the whole laboratory in order to valorize these compounds for other applications whether by virtual screening or physical screening. We have established a protocol (screening – identification – analysis and storage) which allows to manage the synthesized products (intermediate and final) of the last 30 years resulting from projects completed or stopped after the departure of the researchers.
We have 3 chemical libraries that are being evaluated in the laboratory and can be the subject of new collaborative screening projects.

Services

With the technical and financial support of the CN and the laboratory, we have collected about 5,500 products from all teams, creating a structural database managed under IsisBase (sdf files). Of these, 4950 compounds are available for automated screening in the form of 96-well plates or sherry picking.

As part of the CN / SANOFI agreement, a copy of our plates is stored at EVOTEC (Toulouse) and available via the French National Chemical Library and ChemBioFrance.

We also have several 96-well plate sets available for internal screenings and collaborations with screening platforms. At the same time, we undertook the virtual screening of our chemical library with the laboratory’s modeling service (Macromolecular Modeling Platform) in the framework of internal and external collaborations.

VALORIZATION

We currently have 15 external collaborations following the screening of our chemical library via the CN, 5 internal and 10 external internal screening studies. The balance sheet is currently 6 publications and 4 ANR filings.

valorization of a synthetic intermediate

valorisation of chemical library

Main publications

2020
Frei, J. Zuegg, A. G Elliott,   M. V Baker,   S. Braese,   C. Brown,   F. Chen,   C. Gerard Dowson,   G. Dujardin,   N. Jung,   A. Paden King,   A. M. Mansour,   M. Massi,   J. Moat,   H. A Mohamed,   A. Renfrew,   P. Rutledge,   P. J Sadler,   M. Houghton Todd,   C. E. Willans,   J. J. Wilson,   M. Allister Cooper  and  M. Blaskovich  « Metal Complexes as a Promising Source for New Antibiotics »

Chem. Sci., 2020, doi:10.1039/C9SC06460E

2019
S. Hayek , N. Bekaddour, L. Besson, R. Alves de Sousa, N. Pietrancosta, S. Viel, N. Smith, Y. Jacob, S. Nisole, S. Mandal, D. S. Wishart, T. Walzer, J.-P. Herbeuval, P.-O. Vidalain « Identification of Primary Natural Killer Cell Modulators by Chemical Library Screening with a Luciferase-Based Functional »
SLAS Discov. 2019, 24, 25-37. doi: 10.1177/2472555218797078

U. Ashraf, L. Tengo, L. Le Corre, G. Fournier, P. Busca, A. A. McCarthy, M.-A. Rameix-Welti, C. Gravier-Pelletier, R. W. H. Ruigrok, Y. Jacob, P.-O. Vidalain, N. Pietrancosta, T. Crépin, N. Naffakh « Destabilization of the human RED–SMU1 splicing complex as a basis for host-directed antiinfluenza strategy »
PNAS 2019, 116, 10968-10977. DOI:10.1073/pnas.1901214116

2018
P. Laskaris, R. Vicentefranqueira, O. Helynck, G. Jouvion, J. A. Calera, L. du Merle, F. Suzenet, F. Buron, R. Alves de Sousa, D. Mansuy, J.-M. Cavaillon, J.-P. Latgé, H. Munier-Lehmann, O. Ibrahim-Graneta “A novel polyaminocarboxylate compound to treat murine pulmonary aspergillosis by interfering with zinc metabolism” Antimicrob Agents Chemother 2018, 62, 2510-2517. DOI: 10.1128/AAC.02510-17

M. J. Fer, Mickael, L. Le Corre, N. Pietrancosta, N. Evrard-Todeschi, S. Olatunji, A. Bouhss, S. Calvet-Vitale, C. Gravier-Pelletier “Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics” Current Medicinal Chemistry 2018, 25, 6013-6029. DOI:10.2174/0929867325666180330095154

V. Sakanyan. « Reactive Chemicals and Electrophilic Stress in Cancer. » High-Throughput 2018, 7, 12. doi: 10.3390/ht7020012

2016
V. Sakanyan, P. Hulin, R. Alves de Sousa, V. Silva, A. O. Viviane, A. Hambardzumyan, S. Nedellec, C. Tomasoni, C. Loge, C. Pineau, C. Roussakis, F. Fleury, I. Artaud “Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1” Scientific Reports 2016, 6, 21088. DOI: 10.1038/srep21088

V. Sakanyan, F. Benaiteau, R. Alves de Sousa, C. Pineau, I. Artaud “Straightforward Detection of Reactive Compound Binding to Multiple Proteins in Cancer Cells: Towards a Better Understanding of Electrophilic Stress” Ann Clin Exp Metabol  2016, 1, 1006.

2014
V. Sakanyan, M. Angelini, M. Le Bechec, M. F. Lecocq, F. Benaiteau, B. Rousseau, A. Gyulkhandanyan, L. Gyulkhandanyan, C. Loge, E. Reiter, C. Roussakis, F. Fleury “Screening and discovery of nitro-benzoxadiazole compounds activating epidermal growth factor receptor (EGFR) in cancer cells” Scientific reports 2014, 4, 3977. DOI: 10.1038/srep03977

Chemical Library

Staff

Rodolphe Alves De Sousa
Senior Engineer (CNRS)
Contact:

+33 1 42 86 21 93

Presentation chemical library

PRESENTATION

University of Paris Descartes and the Laboratory of Pharmaceutical and Toxicological Chemistry and Biochemistry (LCBPT) are associated to the “Chimiothèque Nationale” (CN) – French National Chemical Library of CNRS since 2004. Our laboratory is located at the chemistry / biology interface with various disciplinary activities. We develop both biologically active molecules for therapeutic purposes but also tools for the characterization of new targets, for the elucidation of biological mechanisms and for imaging. The teams are particularly distinguished in the development of probes and in various spectroscopic techniques such as EPR and NMR for in vitro and in vivo studies. The unit has expertise ranging from synthetic methodology to bioorganic and bioinorganic chemistry. Biological research themes focus mainly on anti-infectives (antibacterials, antivirals), anticancer drugs, the central nervous system, the immune system and toxicology.

Goals

We have established a pool of products of interest, which after verification of their purity, have been integrated into an electronic database common to the whole laboratory in order to valorize these compounds for other applications whether by virtual screening or physical screening. We have established a protocol (screening – identification – analysis and storage) which allows to manage the synthesized products (intermediate and final) of the last 30 years resulting from projects completed or stopped after the departure of the researchers.
We have 3 chemical libraries that are being evaluated in the laboratory and can be the subject of new collaborative screening projects.

Services

With the technical and financial support of the CN and the laboratory, we have collected about 5,500 products from all teams, creating a structural database managed under IsisBase (sdf files). Of these, 4950 compounds are available for automated screening in the form of 96-well plates or sherry picking.

As part of the CN / SANOFI agreement, a copy of our plates is stored at EVOTEC (Toulouse) and available via the French National Chemical Library.

We also have several 96-well plate sets available for internal screenings and collaborations with screening platforms. At the same time, we undertook the virtual screening of our chemical library with the laboratory’s modeling service (http: //www.biomedicale.parisdescartes.fr/ umr8601 / presentation-290.html) in the framework of internal and external collaborations.

VALORIZATION

We currently have 15 external collaborations following the screening of our chemical library via the CN, 5 internal and 10 external internal screening studies. The balance sheet is currently 6 publications and 4 ANR filings.

valorization of a synthetic intermediatevalorisation of chemical library

Main publications

U. Ashraf, L. Tengo, L. Le Corre, G. Fournier, P. Busca, A. A. McCarthy, M.-A. Rameix-Welti, C. Gravier-Pelletier, R. W. H. Ruigrok, Y. Jacob, P.-O. Vidalain, N. Pietrancosta, T. Crépin, N. Naffakh “Destabilization of the human RED–SMU1 splicing complex as a basis for host-directed antiinfluenza strategy”
PNAS 2019, 116, 10968-10977. DOI:10.1073/pnas.1901214116
S. Hayek , N. Bekaddour, L. Besson, R. Alves de Sousa, N. Pietrancosta, S. Viel, N. Smith, Y. Jacob, S. Nisole, S. Mandal, D. S. Wishart, T. Walzer, J.-P. Herbeuval, P.-O. Vidalain “Identification of Primary Natural Killer Cell Modulators by Chemical Library Screening with a Luciferase-Based Functional”
SLAS Discov. 2019, 24, 25-37. doi: 10.1177/2472555218797078
V. Sakanyan. “Reactive Chemicals and Electrophilic Stress in Cancer.” High-Throughput 2018, 7, 12. doi: 10.3390/ht7020012
M. J. Fer, Mickael, L. Le Corre, N. Pietrancosta, N. Evrard-Todeschi, S. Olatunji, A. Bouhss, S. Calvet-Vitale, C. Gravier-Pelletier “Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics” Current Medicinal Chemistry 2018, 25, 6013-6029. DOI:10.2174/0929867325666180330095154
P. Laskaris, R. Vicentefranqueira, O. Helynck, G. Jouvion, J. A. Calera, L. du Merle, F. Suzenet, F. Buron, R. Alves de Sousa, D. Mansuy, J.-M. Cavaillon, J.-P. Latgé, H. Munier-Lehmann, O. Ibrahim-Graneta “A novel polyaminocarboxylate compound to treat murine pulmonary aspergillosis by interfering with zinc metabolism” Antimicrob Agents Chemother 2018, 62, 2510-2517. DOI: 10.1128/AAC.02510-17
V. Sakanyan, F. Benaiteau, R. Alves de Sousa, C. Pineau, I. Artaud “Straightforward Detection of Reactive Compound Binding to Multiple Proteins in Cancer Cells: Towards a Better Understanding of Electrophilic Stress” Ann Clin Exp Metabol  2016, 1, 1006.
V. Sakanyan, P. Hulin, R. Alves de Sousa, V. Silva, A. O. Viviane, A. Hambardzumyan, S. Nedellec, C. Tomasoni, C. Loge, C. Pineau, C. Roussakis, F. Fleury, I. Artaud “Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1” Scientific Reports 2016, 6, 21088. DOI: 10.1038/srep21088
V. Sakanyan, M. Angelini, M. Le Bechec, M. F. Lecocq, F. Benaiteau, B. Rousseau, A. Gyulkhandanyan, L. Gyulkhandanyan, C. Loge, E. Reiter, C. Roussakis, F. Fleury “Screening and discovery of nitro-benzoxadiazole compounds activating epidermal growth factor receptor (EGFR) in cancer cells” Scientific reports 2014, 4, 3977. DOI: 10.1038/srep03977