Ref HAL: hal-00822875_v1
DOI: 10.1039/c2cs35406c
Résumé: Conjugation of oligonucleotides (ONs) to a variety of reporter groups has been the subject of intensive research during the last decade. Conjugation is indeed of great interest because it can be used not only to improve the existing ONs properties but also to impart new ones. In this context tremendous efforts have been made to conjugate carbohydrate moieties to ONs. Indeed carbohydrates play an important role in biological processes such as signal transduction and cell adhesion through the recognition with sugar-binding proteins (i.e. lectins) located on the surface of cells. For this reason, carbohydrate-oligonucleotide conjugates (COCs) have been first developed for improving the poor cellular uptake or tissue specific delivery of ONs through receptor-mediated endocytosis. Besides the targeted ONs delivery, carbohydrate-oligonucleotide conjugates (COCs) are also evaluated in the context of carbohydrate biochips in which surface coating with carbohydrates is achieved by using the DNA-directed immobilization strategy (DDI). Peptide nucleic acids (PNAs) have also been extensively investigated as a surrogate of DNA for diverse applications. Therefore attachment of carbohydrate moieties to this class of molecules has been studied. The aforementioned applications of COCs require mimicking of the natural processes, in which the weak individual protein-carbohydrate binding is overcome by using multivalent interactions. This tutorial review focuses on the recent advances in carbohydrate-oligonucleotide conjugates and describes the major synthetic approaches available. In addition, an overview of applications that have been developed using various scaffolds allowing multivalent interactions is provided. Finally recent results on the use of peptide nucleic acids as oligonucleotides surrogate are described.

Ref HAL: hal-00821045_v1
DOI: 10.1371/journal.pone.0057866
Résumé: Background: The aim of this study was to investigate the molecular mechanisms involved in the production of Th1 cytokines, namely IL-12 and IL-27, when the intra-macrophage redox state was altered by different chemical entities such as GSH-C4, which is reduced glutathione carrying an aliphatic chain, or I-152, a pro-drug of N-acetyl-cysteine (NAC) and betamercaptoethylamine. We had already demonstrated that GSH-C4 and I-152 could shift the immune response towards Th1 in Ovalbumin-immunized mice as well as enhance Th1 response in HIV-1 Tat-immunized mice.

Ref HAL: hal-00821002_v1
DOI: 10.1007/s00706-012-0881-7
Résumé: The development of synthetic systems displaying dynamic and adaptive characteristics is a formidable challenge with wide applications from biotechnology to therapeutics. Recently, we described a dynamic and programmable nucleic acid-based system relying on the formation of reversible boronate internucleosidic linkages. The DNA- or RNA-templated system comprises a 50 -ended boronic acid probe connecting a 30 -ended ribonucleosidic oligonucleotide partner. To explore the dominant factors that control the reversible linkage, we synthesized a series of 30 -end modified ribonucleotidic strands. Evidence suggests that geometric and steric factors are key features for controlling the equilibria.

Ref HAL: hal-00820792_v1
DOI: 10.1039/c3gc40302e
Résumé: This paper describes an original methodology for peptide bond synthesis avoiding toxic solvents and reactants. Ball-milling stoichiometric amounts of Boc-protected α-amino acid N-carboxyanhydrides (Boc-AA-NCA) or Boc-protected α-amino acid Nhydroxysuccinimide esters (Boc-AA-OSu) with α-amino acid alkyl ester salts in the presence of NaHCO3 and a minimal quantity of EtOAc led to the production of di- to pentapeptides in an efficient and environmentally benign manner. This approach was successfully applied to the synthesis of Leu-enkephalin.

Ref HAL: hal-00820777_v1
DOI: 10.1002/adsc.201201047
Résumé: Novel palladium N-heterocyclic-carbene (NHC)-based complexes with 3,4,5-trimethoxybenzyl, alkyl and sulfonate N-substituents were obtained and fully characterized. The new complexes were used as pre-catalysts in the Suzuki-Miyaura coupling of various aryl halides/boron sources in glycerol under pulsed-ultrasound (P-US) activation. High yields were obtained under mild reaction conditions, without formation of undesired by-products. The pure final cross-coupling products were easily recovered without column chromatography and the catalytic/ solvent system could be recycled. TEM (transmission electron microscopy) and XPS (X-ray photoelectron spectroscopy) were used to characterize the nanoparticles and to investigate the fate of the catalysts.

Ref HAL: hal-00809186_v1
PMID 23373770
DOI: 10.1111/jnc.12189
Résumé: Ras-GAP SH3-domain-binding protein, G3BP, is an important component in the assembly of stress granules (SGs), which are cytoplasmic aggregates assembled following translational stress. To assess the physiological function of G3BP, we generated viable G3bp1-knockout (KO) mice, which demonstrated behavioral defects linked to the CNS-associated with ataxia phenotype. Immunohistochemistry pinpointed high expression of G3BP in the cytoplasm of hippocampal neurons and Purkinje cells of the cerebellum of wild-type mice. Also, electrophysiological measurements revealed that the absence of G3BP1 leads to an enhancement of short-term potentiation (STP) and long-term depression in the CA1 area of G3bp1 KO mice compared with wild-type mice. Consistently, G3BP1 deficiency in neurons leads to an increase in intracellular calcium and calcium release in response to (S)-3,5-Dihydroxyphenylglycine, a selective agonist of group I metabotropic glutamate receptors. These results show, for the first time, a requirement for G3BP1 in the control of neuronal plasticity and calcium homeostasis and further establish a direct link between SG formation and neurodegenerative diseases.

Ref HAL: hal-00809177_v1
PMID 23478644
DOI: 10.1038/pr.2013.40
Résumé: Background:Prenatal infection is a major risk factor for the occurrence of neuropsychiatric disorders. These have been associated with hippocampal neuroanatomical and functional abnormalities. In the present study, we evaluated the occurrence of pyramidal cell disarray and reelin neuronal deficit in the hippocampus, and the protective role of N-acetyl-cysteine (NAC) in a rodent experimental model of prenatal immune challenge.Methods:Sprague-Dawley rats received either 500 μg/kg of endotoxin (lipopolysaccharide, LPS) or 2 ml/kg of isotonic saline by i.p. injection on day 19 of gestation. After LPS injection, rats were or were not maintained on a preventive treatment of NAC (5 g/l in tap water), up to delivery. The pyramidal cell orientation and the number and type of reelin-expressing neurons were determined in male offspring.Results:Prenatal LPS challenge led to permanent pyramidal cell disarray and to an early and transient decreased density of reelin-immunoreactive neurons. These disorders, more pronounced in the CA3 area, were prevented by NAC.Conclusion:Hippocampal cytoarchitectural alterations and reelin deficiency may be involved in the development of remote cognitive impairments in this model. The antioxidant NAC is an efficient neuroprotective drug that underlines the role of oxidative stress in prenatal infection and associated neurodevelopmental damage.Pediatric Research (2013); doi:10.1038/pr.2013.40.