Directing peptide crystallization through curvature control of nanotubes ‡

International audienceIn the absence of efficient crystallization methods, the molecular structures of fibrous assemblies have so far remained rather elusive. In this paper, we present a rational method to crystallize the lanreotide octapeptide by modification of a residue involved in a close contact. Indeed, we show that it is possible to modify the curvature of the lanreotide nanotubes and hence their diameter. This fine tuning leads to crystallization because the radius of curvature of the initially bidimensional peptide wall can be increased up to a point where the wall is essentially flat and a crystal is allowed to grow along a third dimension. By comparing X-ray diffraction data and Fourier transform Raman spectra, we show that the nanotubes and the crystals share similar cell parameters and molecular conformations, proving that there is indeed a structural continuum between these two morphologies. These results illustrate a novel approach to crystallization and represent the first step towards the acquisition of an Å-resolution structure of the lanreotide nanotubes β-sheet assembly

Regioselective Halogenation of 1,4-Benzodiazepinones via CH Activation

International audienceThis article reports an efficient CH activation process for regioselective halogenation of 1,4-benzodiazepinones. Direct halogenation with NXS (X = Br, I) affords halogenated benzodiazepinones on the central aromatic ring whereas catalyst (Pd(OAc) 2) controlled CH activation furnishes regioselectively ortho halogenated benzodiazepinones on the phenyl side chain

Pyrrolotriazinone as an Underexplored Scaffold in Drug Discovery

International audienceHeterocyclic amino derivatives have been extensively synthesized and validated as potent bioactive compounds, and nowadays, numerous marketed drugs share these scaffolds, from very simple structures (monoamino, monocyclic compounds) to much more complex molecules (polycyclic derivatives with two or more nitrogen atoms within the (fused) rings). In a constant quest for new chemical entities in drug discovery, a few novel heterocycles have emerged in recent years as promising building blocks for the obtainment of bioactive modulators. In this context, pyrrolotriazinones have attracted attention, and some show promising biological activities. Here, we offer an extensive review of pyrrolo[2,1-f][1,2,4]triazin-4(1H)-one and pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one, describing their biological properties en route to drug discovery.</jats:p

Synthèse de Nouvelles Molécules Cages et Applications pour l'Imagerie par RMN Xénon.

L'Imagerie par Résonance Magnétique (IRM) est une technique d imagerie très utilisée de nos jours, notamment pour le diagnostic médical. L utilisation d agents de contraste lors d un examen IRM permet d obtenir des images de bonne qualité. Cependant, le manque de sensibilité de cette technique d imagerie a conduit à l utilisation d espèces hyperpolarisées (3He, 13C, 129Xe) en IRM. Le xénon (Xe) apparait aujourd hui comme un composé très prometteur pour de telles applications mais son manque de sélectivité rend l imagerie moléculaire impossible. Le développement et l utilisation de molécules cages capable d encapsuler le xénon et de l amener vers la cible à imager est donc indispensable. Dans ce contexte, nous nous sommes intéressés au cours de cette thèse à l élaboration de telles molécules, et plus précisément, à l obtention de nouveaux cryptophanes qui présentent la plus forte affinité pour le xénon afin de pouvoir utiliser ces molécules en tant qu outils pour l IRM Xe. Une nouvelle voie de synthèse du cryptophane ayant la plus grande affinité pour le xénon a été mise au point ; ce composé a été fonctionnalisé pour la première fois au laboratoire et ceci dans le but d obtenir les premières biosondes dérivées de composé. Le greffage d antenne de reconnaissance sur ces biosondes permettrait alors de faire de l imagerie ciblée. Une sonde pour la détection du peroxyde d hydrogène (H2O2) a été synthétisée. Le peroxyde d hydrogène est impliqué dans le développement de stress oxydant cellulaire et présent en ces de maladies neurodégénératives (Parkinson, Alzheimer). La sonde obtenue a permis d imager H2O2 par IRM Xe pour la première fois. Un hybride composé de nanotube de carbone et de cryptophanes a aussi été synthétisé en vue de disposer d outil présentant une forte concentration de cryptophanes et d améliorer la sensibilité de la technique d imagerie utilisant du xénon.Magnetic Resonance Imaging (MRI) is widely used today for early medical diagnosis. During the MRI examination, the use of contrast agent allows the obtention of well resolved images. However the lack of sensibility of this technic lead to the utilization of hyperpolarized species (3He, 13C, 129Xe) in MRI. The xenon (Xe) is the more promising but due to its weak selectivity, it cannot be used in molecular imaging. So, the development and utilization of host molecules able to encapsulate the xenon and bring it to a targeted biological tissue or organ is necessary. In these conditions, during this thesis, we worked on the elaboration of such molecules, and particularly, in cryptophanes since these compounds have strong affinity for xenon and could be used as tools for MRI by hyperpolarized xenon (Hp Xe). A new route synthesis of cryptophane-111, that has the highest affinity for xenon, was developed; first functionalized derivatives of this compound have been also obtained in order to obtain the first biosensors based on cryptophane-111. The coating of specific ligand on these functionalized compounds could allow targeted MRI. A probe for hydrogen peroxide (H2O2) detection was synthesized. Hydrogen peroxide is implicated in cellular oxidative stress and present in case of neurodegeneratives diseases (Parkinson, Alzheimer). The probe obtained allowed the imaging of H2O2 by MRI Xe for the first time. Nanotubes functionalized with strong concentration of cryptophane have been synthesized in order to increase the sensitivity of the imaging technic that uses xenon.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Photochemical Strain-Release Driven Cyclobutylation of C(sp3)-Centered Radicals

Our manuscript describes a photoredox-catalyzed decarboxylative radical addition approach to functionalized cyclobutanes. The reaction involves an unprecedented formal Giese-type addition of C(sp3)-centered radicals to highly strained bicyclo[1.1.0]butanes. The mild photoredox conditions, which make use of a readily available and bench stable phenyl sulfonyl bicyclo[1.1.0]butane, proved to be amenable to a diverse range of α-amino and α-oxy carboxylic acids, providing a concise access to 1,3-disubstituted cyclobutanes. Furthermore, kinetic studies and DFT calculations unveiled mechanistic details on bicyclo[1.1.0]butane reactivity relative to the corresponding olefin system

Photochemical Strain‐Release‐Driven Cyclobutylation of C(sp 3

International audienceAbstract A new photoredox‐catalyzed decarboxylative radical addition approach to functionalized cyclobutanes is described. The reaction involves an unprecedented formal Giese‐type addition of C(sp 3 )‐centered radicals to highly strained bicyclo[1.1.0]butanes. The mild photoredox conditions, which make use of a readily available and bench stable phenyl sulfonyl bicyclo[1.1.0]butane, proved to be amenable to a diverse range of α‐amino and α‐oxy carboxylic acids, providing a concise route to 1,3‐disubstituted cyclobutanes. Furthermore, kinetic studies and DFT calculations unveiled mechanistic details on bicyclo[1.1.0]butane reactivity relative to the corresponding olefin system

Acylated and non-acylated anthocyanins as antibacterial and antibiofilm agents

International audienceAbstractNatural products have served as an essential source of medicinal compounds in drug discovery, with their high abundance in nature and structural complexity being beneficial for various biological activities. Anthocyanins are a natural food colourant that belongs to the flavonoid group of compounds responsible for the colour of various fruits, vegetables, and flowers. There has been a growing interest in these compounds, especially for their health benefits. Antimicrobial resistance is on the rise, making the prognosis for bacterial infection treatment rather difficult. The discovery of alternative agents and treatment approaches is needed. Many in vitro and some in vivo studies demonstrated the potential effects of anthocyanins or their fraction from various natural sources to prevent and treat bacterial infections and biofilm formation. This review reports the recent literature and focuses on the potential role of anthocyanins and their acylation or functional groups for antibacterial and antibiofilm activities and their use as potential antibiotic substitutes or adjuvants. Their possible mechanism of action and prospects of their uses are also discussed.</jats:p