Tetraphenylethylene-based glycoclusters with aggregation-induced emission (AIE) properties as high-affinity ligands of bacterial lectins

International audienceTetraphenylethylene (TPE) is fluorescent through aggregation induced emission (AIE) in water. Herein, TPE was used as the core of glycoclusters that target the bacterial lectins LecA and LecB of Pseudomonas aeruginosa. Synthesis of these TPE-based glycoclusters was accomplished by using azide-alkyne "click" chemistry. The AIE properties of the resulting glycoclusters could be readily verified, but imaging could not be pursued due to the overlap of the fluorescence signals from cells and bacteria. Nonetheless, the glycoclusters displayed nanomolar affinities toward LecA and LecB. Further evaluation in a cell-based anti-adhesive assay highlighted a limited decrease in adhesion (20%) for the fucosylated glycocluster. This confirmed that these TPE-based glycoclusters are indeed LecA and LecB high-affinity ligands. Nevertheless, the hypotheses involving their application in imaging or anti-adhesive therapy could not be verified

Glycogen phosphorylase inhibitors : a patent review (2013-2015)

International audienceIntroduction: Control of glycemia is crucial in the treatment of type 2 diabetes complications. Glycogen phosphorylase (GP) releases glucose from the liver into the blood stream. Design of potent GP inhibitors is a therapeutic strategy in the context of type 2 diabetes.Areas covered: Glucose-based inhibitors have found potential applications since they now reach low nanomolar Ki values. Another set of patents disclose cholic acid/7-aza-indole conjugates for targeted drug delivery to the liver. A series of benzazepinones have also been reported as potent GP inhibitors. In vitro data are reported for GP inhibition but the in vivo biological data at the cellular or animal levels are often missing, even though the literature reported for these molecules is also discussed.Expert opinion: A structural analogy between glucose-based GP inhibitors and C-glucosides targeting sodium glucose co-transporter 2 (SGLT2) is intriguing. Cholic acid/7-aza-indole conjugates are promising in vivo drug delivery systems to the liver. Benzazepinones were very recently described and no associated literature is available, making it very difficult to comment at present. While industry has slowed down on GP inhibitors design, academic groups are pursuing investigations and have provided potential drug candidates which will resuscitate the interest for GP, including its potential for targeting cancer

Synthesis and pharmacological evaluation of benzannulated derivatives as potent and selective sigma-1 protein ligands

International audienceThe σ1 proteins are considered to be a new class of target structures for several central nervous system disorders, including depression, anxiety, psychosis, and Parkinson's and Alzheimer's diseases. Recently, the involvement of these receptors in neuropathic pain and cancer has also been observed. So far, only a few ligands are in clinical trials. In a continuation of our previous studies on the development of σ1 ligands, a new series of benzannulated heterocycles was designed and synthesised. In vitro competition binding assays showed that many of them possessed high σ1 receptor affinity (Ki = 0.6–10.3 nM), and good σ2/σ1 subtype selectivity, without cytotoxic effects on SY5Y cells (human neuroblastoma cell line)

Chirality sensing and discrimination of lysine derivatives in water with a dyn[4]arene

International audienceThe asymmetric deformation of a dyn[4]arene upon the binding of various lysine derivatives leads to distinct induced circular dichroism outputs in buffered water, which can be exploited not only for the determination of their enantiomeric excesses, but also for their classification by linear discriminant analysis

Carboline- and phenothiazine-derivated heterocycles as potent SIGMA-1 protein ligands

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3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

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Diastereoselective Synthesis of a Dyn[3]arene with Distinct Binding Behaviors toward Linear Biogenic Polyamines

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Perylenediimide-based glycoclusters as high affinity ligands of bacterial lectins: synthesis, binding studies and anti-adhesive properties

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Wetting the lock and key enthalpically favours polyelectrolyte binding

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