Ludovic Chaput

French Institute of Health and Medical Research | Inserm

The adsorption of water and substrate on immobilized Candida antarctica lipase B was studied by performing adsorption isotherm measurements and using inverse gas chromatography (IGC). Water adsorption isotherm of the immobilized enzyme showed singular profile absorption incompatible with the Brunauer-Emmet-Teller model, probably due to the hydropho...

Kinetic resolution of pentan-2-ol by CALB catalyzed enantioselective transesterification, with various alkylpropanoate acyl donors, was studied in a solid-gas reactor. Results show that the leaving alkoxy group influences the enantiomeric ratio of the reaction. Resolution of pentan-2-ol with methyl propanoate gives an enantiomeric ratio of 62. Este...

Using the D3R Grand Challenge 4 dataset containing Beta-secretase 1 (BACE) and Cathepsin S (CatS) inhibitors, we have evaluated the performance of our in-house docking workflow that involves in the first step the selection of the most suitable docking software for the system of interest based on structural and functional information available in pu...

Acetylcholinesterase (AChE) is currently the most favorable target for the symptomatic treatment and reduction of Alzheimer's disease (AD). In order to identify new potent inhibitors of this enzyme, we describe herein a new structure‐based virtual screening (SBVS) using the Institut Curie‐CNRS chemical library (ICCL), which contained at the screeni...

During the last few years, we have developed a docking protocol involving two steps: (i) the choice of the most appropriate docking software and parameters for the system of interest using structural and functional information available in public databases (PDB, ChEMBL, PubChem Assay, BindingDB, etc.); (ii) the docking of ligand dataset to provide...

Six novel probes were prepared by covalent attachment of a G4‐DNA ligand (PDC) to various coumarin or pyrene fluorophores. In the absence of DNA, the fluorescence of all probes is quenched due to intramolecular photoinduced electron transfer (PET) evidenced by photophysical and electrochemical studies, molecular modeling and DFT calculations. All p...

Background In drug design, an efficient structure-based optimization of a ligand needs the precise knowledge of the protein–ligand interactions. In the absence of experimental information, docking programs are necessary for ligand positioning, and the choice of a reliable program is essential for the success of such an optimization. The performance...

Background: In a structure-based virtual screening, the choice of the docking program is essential for the success of a hit identification. Benchmarks are meant to help in guiding this choice, especially when undertaken on a large variety of protein targets. Here, the performance of four popular virtual screening programs, Gold, Glide, Surflex and...

Background: In drug design, one may be confronted to the problem of finding hits for targets for which no small inhibiting molecules are known and only low-throughput experiments are available (like ITC or NMR studies), two common difficulties encountered in a typical academic setting. Using a virtual screening strategy like docking can alleviate...

Candida antarctica lipase B (CALB) is characterized by its stability and ease of production and is widely used in the pharmaceutical industry. Here we report on the enantioselectivity of the enzyme using both experimental and computational methods. The apparent kinetic parameters were first experimentally determined for enantiopure butan-2-ol and p...

The lipase B from Candida antarctica is an enzyme displaying enantioselective properties which are interesting to obtain enantio pure compounds by kinetic resolution of racemic mixtures, which are used as pharmaceutical intermediates and fine chemicals. Indeed, for most of the drugs, only one of the two chiral formsis efficient as bioactive compoun...