Publications

The aim of this study was to investigate the permeation properties of 20 permanently positive charged molecules in the parallel artificial membrane permeability assay (PAMPA). Eight of them were derivatives of the N-alkyl-isoquinolinium salt and 12 were congeners of the dye rhodamine 110. Five out of 12 molecules from the rhodamine 110 series have one […]

High-throughput screening (HTS) is the primary technique for new lead identification in drug discovery and chemical biology. Unfortunately, it is susceptible to false-positive hits. One common mechanism for such false-positives is the congregation of organic molecules into colloidal aggregates, which nonspecifically inhibit enzymes. To both evaluate the feasibility of large-scale identification of aggregate-based inhibition and […]

High throughput screening (HTS) data is often noisy, containing both false positives and negatives. Thus, careful triaging and prioritization of the primary hit list can save time and money by identifying potential false positives before incurring the expense of followup. Of particular concern are cell-based reporter gene assays (RGAs) where the number of hits may […]

In order to develop a fluorescence polarization (FP) assay for calcium binding proteins, a fluorescent peptides based library of 1328 compounds has been synthesized. The use of this library has been validated by setting up a FP-high-throughput screening (FP-HTS) assay for calmodulin using the synthetic gene product (synCaM). With this assay, a set of 880 […]

Advances in genetics, proteomics and cell biology over the past 20 years have unearthed a multitude of potential macromolecular targets for the selective treatment of disease. The challenge remains to find appropriate small molecule ligands for these proteins (or nucleic acids), and to use these ligands to validate novel disease targets. The advent of low-cost […]

BACKGROUND: A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed […]

Bacterial secondary metabolites display diverse biological activities, thus having potential as pharmacological agents. Although most of these compounds are discovered by random screening, it is possible to predict and re-design their structures based on the information on their biosynthetic pathways. Biosynthesis of macrolides, governed by modular polyketide synthases (PKS), obeys certain rules, which can be […]

A survey of novel small-molecule therapeutics reveals that the majority of them result from analogue design and that their market value represents two-thirds of all small-molecule sales. In natural science, the term analogue, derived from the Latin and Greek analogia, has always been used to describe structural and functional similarity. Extended to drugs, this definition […]

Novel inhibitors of Trypanosoma brucei and mammalian UDP-Glc 4???-epimerase were identified by screening a small library of natural products and commercially available drug-like molecules. The inhibitors possess low micromolar potency against the T. brucei and human enzymes in vitro, display a degree of selectivity between the two enzymes, and are cytotoxic to cultured T. brucei […]