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Jean Herscovici

Publications and source records attributed to Jean Herscovici.

12 recordsLinked to original sources
PubMed2006

Reusable polymer-supported catalyst for the [3+2] Huisgen cycloaddition in automation protocols.

[reaction: see text] A polymer-supported catalyst for Huisgen's [3+2] cycloaddition reaction between azides and alkynes was prepared from copper(I) iodide and Amberlyst A-21. This catalyst was then used in an automated synthesis of 1,4-disubstituted 1,2,3-triazoles giving access to these products in good yields. The catalyst has shown good activity, stability, and recycling capabilities.

Journal Article↗
PubMed2005

Sialyl Lewis(x) analogs based on a quinic acid scaffold as the fucose mimic.

(-)-Quinic acid was used as a starting material for the preparation of sialyl Lewis(x) mimetics in order to target E-selectin. Spatial orientation of the hydroxyl groups of quinic acid could mimic the l-fucose ones. Introduction of a side chain ending with a carboxylic acid was effected to replace the sialic acid interaction at the carbohydrate recognition domain. A first series of derivatives, incorporating amino acids linked to quinic acid, were tested for their affinity and found to interact with E-selectin with IC(50) within the millimolar range.

Cell Adhesion↗
PubMed2005

New short route to unsaturated fluoroketonucleosides: case of 5-fluoro-1-(6-O-acetyl-3,4-di-deoxy-3-fluoro-beta-D-glycero-hex-3-eno-pyranos-2-ulosyl) uracil.

The proposed short synthesis involves two key steps: Oxidation of the isopropylidene derivative of the 3-fluoronucleoside possessing a free hydroxyl group in 2-position and acetylation of deprotected 3-fluoro-2-ketonucleoside which, after a beta-elimination reaction, gives the desired unsaturated ketonucleoside 5.

Chromatography, Thin Layer↗
PubMed2002

Synthesis of 3-C-(6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-mannopyranosyl)-1-propene: a caveat.

During the preparation of 3-C-(6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-mannopyranosyl)-1-propene, using a published Sakurai-type reaction on the parent methyl glycoside, some observations were made on the sensitivity to reaction conditions that were not previously reported. This Note presents the study of this allylation reaction followed by acetolysis, which ultimately led to the best conditions to obtain the C-glycoside, and on further transformations to yield the corresponding aldehydic and acidic derivatives.

Acetylation↗
PubMedDate not supplied

Design, synthesis, and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes.

Gadolinium-chelating cationic lipids have been synthesized to obtain lipoplexes with MRI contrast properties. These compounds were designed to follow the biodistribution of synthetic DNA for gene delivery by nuclear magnetic resonance imaging. The lipid MCO-I-68 was synthesized, and chelate complexes with gadolinium were formed and characterized in terms of physicochemical and DNA binding properties. The transfection activity of MCO-I-68-Gd/DNA complexes was assayed in vitro on NIH 3T3. Different formulations of the product were tested. When up to 5% of the gadolinium lipid complexes were co-formulated with the cationic lipid RPR120535 used as a reference, the transfection levels were maintained as compared to RPR120535 alone. To date, only a liposomal formulation of a gadolinium-cationic lipid chelate without DNA had been observed using magnetic resonance imaging. In vivo intratumoral administration of MCO-I-68-Gd/DNA lipoplexes to tumor model led to an important increase of the NMR signal. It was demonstrated that the new complexes also acted as transfection carriers when they were formulated from liposomes.

3T3 Cells↗
PubMedDate not supplied

DNA complexing lipopolythiourea.

We present a neutral lipopolythiourea (DTTU) as a potential DNA-binding agent. Light scattering experiments showed that mixing a lipopolythiourea with dipalmitoylphosphatidylcholine (DPPC/DTTU) led to small particles with sizes ranging from 100 to 150 nm at optimum conditions. Setting a fixed DNA amount, an increasing amount of DTTU/DPPC or DPPC lipids was added. Particle size increased only with DTTU/DPPC, indicating that interaction occurred between the DTTU/DPPC particles and DNA. In the same way, only DTTU/DPPC limited the ethidium bromide accessibility to plasmid DNA. These data suggest that DTTU/DPPC liposomes associate to DNA, which was confirmed by agarose gel experiments. To prove the active part of the DTTU lipid itself in DNA compaction, pegoylated-lipid was used. Cholesterol-PEG(2000) alone was not able to condense DNA. In contrast, DTTU/PEG-cholesterol was able to retain plasmid DNA on an agarose gel. In vivo injection of DTTU/DPPC/complexes was studied. Circulation time increase for noncationic particles as compared to cationic. More obvious was the lack of nonspecific accumulation in the lung, where a gain of 3 to 40 fold was measured.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

Design, synthesis, and evaluation of enhanced DNA binding new lipopolythioureas.

Nonviral gene delivery is limited to a large extent by the cationic nature of most of the chemical vector. We have shown that lipopolythioureas interact with DNA. However, lipopolythioureas were not very efficient at transfecting cells, probably due to reduced interaction between the noncationic synthetic lipid and the cell membrane. Here, we report that liposomes made from a new thiourea lipid, DPPC, and a lipid bearing an RGD ligand allowed very efficient entry of the lipopolythioureas into integrin alpha(v)beta(3) expressing cells. In addition, we show that a stable interaction between DNA and lipopolythiourea could be obtain with two thiourea groups. Moreover, the addition of a hydrophilic terminus improves the formulation of these new DNA binding agents.

Animals↗
PubMedDate not supplied

Fast, easy, and efficient method for the purification of phenolic isomers using a selective solid-phase scavenging process.

The need for fast and efficient purification methods that can be easily handled and moreover automated is considerably increasing with the new techniques of high-throughput chemical synthesis. Following our previous work on the use of simple polymeric scavengers in fast reactions and purifications of organic substances, this article presents the results found during the development of a new method for the purification of phenolic substances. The purification method was found to be regulated by the interaction of acidic phenol groups with a basic polystyrene resin. Furthermore, the scavenging of phenolic isomers proved to be very selective for a given isomer. But the most interesting aspect of this method is that it is based on a simple contact in situ with the resin and that the adsorption/desorption process of the phenol was found to be solvent-dependent. The phenols can thus be freed from impurities, or other isomers, by a simple and fast contact with the resin in the first solvent, filtration, and washings, followed by liberation of the purified phenol by a last soaking in another solvent for desorption. The method was successfully applied to the purification of a crude reaction mixture issued from the Fries rearrangement of phenyl acetate, as well as to small libraries of phenolic derivatives.

Journal Article↗
PubMedDate not supplied

Optimization of cationic lipid mediated gene transfer: structure-function, physico-chemical, and cellular studies.

The rationale design aimed at the enhancement of cationic lipid mediated gene transfer is discussed. These improvements are based on the straight evaluation of the structure-activity relationship and on the introduction of new structures. Much attention have been given to the supramolecular structures of the lipid/DNA complexes, to the effect of serum on gene transfer and to the intracellular trafficking of the lipoplexes. Finally new avenue using reducible cationic lipids has been discussed.

3T3 Cells↗