Aurélien Lesnard
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Aurélien Lesnard has a total of 13 co-authors. Here are the top co-authors by number of shared publications:
- Anne Brelot
Institut Pasteur, Université Paris Cité, CNRS UMR3569, Virus and Immunity Unit
1 shared publication - Bernard Lagane
Institut National de la Santé et de la Recherche Médicale Unit 1108, Viral Pathogenesis Unit, Department of Virology, Institut Pasteur, 75015 Paris, France
1 shared publication - Fanny Fontaine
Department of Clinical Biochemistry, CHU Caen Normandie, CS 30001, 14033 Caen Cedex, France
1 shared publication - Fernando Arenzana-Seisdedos
Viral Pathogenesis Unit, Department of Virology, Institut Pasteur, 75015 Paris, France
1 shared publication - Hélène Munier-Lehmann
Université Paris Cité, INSERM, Health & Functional Exposomics - HealthFex, U1124, Institut Pasteur, Structural Biology and Chemistry Department, F-75006 Paris, France
1 shared publication - Isabelle Staropoli
Institut Pasteur
1 shared publication
Latest Publications
- Open Access
Discovery of Bis-Imidazoline Derivatives as New CXCR4 Ligands
The chemokine receptor CXCR4 and its ligand CXCL12 regulate leukocyte trafficking, homeostasis and functions and are potential therapeutic targets in many diseases such as HIV-1 infection and cancers. Here, we identified new CXCR4 ligands in the CERMN chemical library using a FRET-based high-throughput screening assay. These are bis-imidazoline compounds comprising two imidazole rings linked by an alkyl chain. The molecules displace CXCL12 binding with submicromolar potencies, similarly to AMD3100, the only marketed CXCR4 ligand. They also inhibit anti-CXCR4 mAb 12G5 binding, CXCL12-mediated chemotaxis and HIV-1 infection. Further studies with newly synthesized derivatives pointed out to a role of alkyl chain length on the bis-imidazoline properties, with molecules with an even number of carbons equal to 8, 10 or 12 being the most potent. Interestingly, these differ in the functions of CXCR4 that they influence. Site-directed mutagenesis and molecular docking predict that the alkyl chain folds in such a way that the two imidazole groups become lodged in the transmembrane binding cavity of CXCR4. Results also suggest that the alkyl chain length influences how the imidazole rings positions in the cavity. These results may provide a basis for the design of new CXCR4 antagonists targeting specific functions of the receptor.
Open AccessDiscovery of Bis-Imidazoline Derivatives as New CXCR4 Ligands
The chemokine receptor CXCR4 and its ligand CXCL12 regulate leukocyte trafficking, homeostasis and functions and are potential therapeutic targets in many diseases such as HIV-1 infection and cancers. Here, we identified new CXCR4 ligands in the CERMN chemical library using a FRET-based high-throughput screening assay. These are bis-imidazoline compounds comprising two imidazole rings linked by an alkyl chain. The molecules displace CXCL12 binding with submicromolar potencies, similarly to AMD3100, the only marketed CXCR4 ligand. They also inhibit anti-CXCR4 mAb 12G5 binding, CXCL12-mediated chemotaxis and HIV-1 infection. Further studies with newly synthesized derivatives pointed out to a role of alkyl chain length on the bis-imidazoline properties, with molecules with an even number of carbons equal to 8, 10 or 12 being the most potent. Interestingly, these differ in the functions of CXCR4 that they influence. Site-directed mutagenesis and molecular docking predict that the alkyl chain folds in such a way that the two imidazole groups become lodged in the transmembrane binding cavity of CXCR4. Results also suggest that the alkyl chain length influences how the imidazole rings positions in the cavity. These results may provide a basis for the design of new CXCR4 antagonists targeting specific functions of the receptor.