Search results for "DISCOVERY"
showing 10 items of 4119 documents
Hemmung der Fettsäureoxydation als ein Faktor bei der antiketogenen Wirkung von Zuckern und Polyalkoholen
1966
Die Wirkung von Fructose, Glucose, Sorbit, Xylit, Ribit und Glycerin auf die Oxydation von14C-Palmitinsaure durch gesunde und diabetische Ratten wurde untersucht. Die uber die Norm gesteigerte Fettsaureoxydation bei diabetischen Tieren wird durch Dauerinfusion aller untersuchten Kohlenhydrate mit Ausnahme von Glucose signifikant gehemmt. Die starkste Wirkung hat Sorbit; dann folgen Xylit, Fructose und Glycerin; Ribit hat die schwachste Wirkung.
Pertussis in adults with persistent cough: a prospective follow up study in primary care.
2009
Despite high coverage of pertussis vaccine, B. pertussis has remained endemic and adults are recognized as reservoir for infection among incompletely immunized infants. Between November 15th 2004 and November 14th 2006, 37 general practitioners, attending 56,658 adults, recruited all patients with persistent cough. A diagnosis of pertussis was considered in those with an unexplained cough, lasting 14 or more days and a positive polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) IgG anti-Pertussis Toxin (PT). During the period of the study 86 patients presented with persistent cough (106 cases per 100,000 person-years). According to laboratory criteria, 35% were cla…
Resolving Binding Events on the Multifunctional Human Serum Albumin
2020
Abstract Physiological processes rely on initial recognition events between cellular components and other molecules or modalities. Biomolecules can have multiple sites or mode of interaction with other molecular entities, so that a resolution of the individual binding events in terms of spatial localization as well as association and dissociation kinetics is required for a meaningful description. Here we describe a trichromatic fluorescent binding‐ and displacement assay for simultaneous monitoring of three individual binding sites in the important transporter and binding protein human serum albumin. Independent investigations of binding events by X‐ray crystallography and time‐resolved dyn…
Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the …
2021
A water-soluble fluorescent aza-BODIPY platform (Wazaby) was prepared and functionalized by a polyazamacrocycle agent and a bioconjugable arm. The resulting fluorescent derivative was characterized and bioconjugated onto a trastuzumab monoclonal antibody as a vector. After bioconjugation, the imaging agent appeared to be stable in serum (>72 h at 37 °C) and specifically labeled HER-2-positive breast tumors slices. The bioconjugate was radiolabeled with [111In] indium and studied in vivo. The developed monomolecular multimodal imaging probe (MOMIP) is water-soluble and chemically and photochemically stable, emits in the near infrared (NIR) region (734 nm in aqueous media), and displays a goo…
Cellular imaging using BODIPY-, pyrene- and phthalocyanine-based conjugates
2017
International audience; Fluorescent Probes aimed at absorbing in the blue/green region of the spectrum and emitting in the green/red have been synthesized (as the form of dyads-pentads), studied by spectrofluorimetry, and used for cellular imaging. The synthesis of phthalocyanine-pyrene 1 was achieved by cyclotetramerization of pyrenyldicyanobenzene, whereas phthalocyanine-BODIPY 2c was synthesized by Sonogashira coupling between tetraiodophthalocyanine and meso-alkynylBODIPY. The standard four-steps BODIPY synthesis was applied to the BODIPY-pyrene dyad 3 starting from pyrenecarbaldehyde and dimethylpyrrole. H-1, C-13, F-19, (BNMR)-B-11, ICP, MS, and UV/Vis spectroscopic analyses demonstra…
Development of peptidomimetic boronates as proteasome inhibitors.
2013
Abstract Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (β5), trypsin-like (β2) and caspase-like (β1). Most important for the development of effective antitumor agents is the inhibition of the β5 subunits. In this context, the dipeptide boronate bortezomib (Velcade ® ) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide bor…
The influence of fluorine position on the properties of fluorobenzoxaboroles
2015
5-Fluoro-2,1-benzoxaborol-1(3H)-ol, a potent antifungal drug also known as Tavaborole or AN2690, has been compared with its three isomers in terms of its activity against several fungi as well as pKa and multinuclear NMR characterization. The molecular and crystal structure of 6-fluoro-2,1-benzoxaborol-1(3H)-ol was determined and compared with that of AN2690.
Near-infrared emitting fluorescent homobimetallic gold(I) complexes displaying promising in vitro and in vivo therapeutic properties
2021
International audience; Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based o…
Gold( i )–BODIPY–imidazole bimetallic complexes as new potential anti-inflammatory and anticancer trackable agents
2017
International audience; Two new gold(I)–BODIPY–imidazole based trackable therapeutic bimetallic complexes have been synthesized and fully characterized. They display strong antiproliferative properties on several types of cancers including colon, breast, and prostate and one of them presents a significant anti-inflammatory effect. Additionally, the two compounds could be visualised in vitro by confocal microscopy in the submicromolar range.
Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR
2014
International audience; : Transverse and longitudinal relaxation times (T1ρ and T1 ) have been widely exploited in NMR to probe the binding of ligands and putative drugs to target proteins. We have shown recently that long-lived states (LLS) can be more sensitive to ligand binding. LLS can be excited if the ligand comprises at least two coupled spins. Herein we broaden the scope of ligand screening by LLS to arbitrary ligands by covalent attachment of a functional group, which comprises a pair of coupled protons that are isolated from neighboring magnetic nuclei. The resulting functionalized ligands have longitudinal relaxation times T1 ((1) H) that are sufficiently long to allow the powerf…