Sandrine Gerber-Lemaire

Harmonic nanocrystals for biolabeling: a survey of optical properties and biocompatibility.

Nonlinear optical nanocrystals have been recently introduced as a promising alternative to fluorescent probes for multiphoton microscopy. We present for the first time a complete survey of the properties of five nanomaterials (KNbO(3), LiNbO(3), BaTiO(3), KTP, and ZnO), describing their preparation and stabilization and providing quantitative estimations of their nonlinear optical response. In the light of their prospective use as biological and clinical markers, we assess their biocompatibility on human healthy and cancerous cell lines. Finally, we demonstrate the great potential for cell imaging of these inherently nonlinear probes in terms of optical contrast, wavelength flexibility, and signal photostability.

Scavenging Free Radicals To Preserve Enhancement and Extend Relaxation Times in NMR using Dynamic Nuclear Polarization

This enhance-ment arises from thermal mixing, which is brought about bymicrowavesaturationoftheEPRtransitionsofstableradicalsthat are mixed with the sample under investigation beforefreezing. In dissolution DNP, the sample is usually polarizedat low temperatures and moderate magnetic fields (T=1.2 Kand B

Glycosylation Pathways as Drug Targets for Cancer: Glycosidase Inhibitors

The combined and ordered sequential action of glycosidases and glycosyltransferases in mammalian cell compartments leads to the addition of defined glycans to proteins and lipids. Altered glycosylation patterns, neoexpression, underexpression or overexpression of glycans are a hallmark of cancer. These changes are either found in the core or the terminal structures of the carbohydrates of glycoproteins. Affected proteins can be either cellular, cell-surface or secreted proteins, and glycosylation modifications frequently result in a modified expression, metabolism, functions, properties, stability and/or cellular localization of glycoproteins in cancer cells, resulting in part in their uncontrolled growth and aggressive behavior. Therefore glycosylation pathways, and the glycosidases and glycosyltransferases of these pathways, represent potential innovative modalities for drug development in cancer therapies which are just beginning to be explored. This review proposes to summarize the published information for glycosidases and their inhibitors in cancer.

Inhibitors of Prolyl Oligopeptidases for the Therapy of Human Diseases: Defining Diseases and Inhibitors

Keywords: Prolyl oligopeptidase inhibitors ; neurological disorders ; peptidomimetics Reference EPFL-ARTICLE-148691doi:10.1021/jm901104gView record in Web of Science Record created on 2010-05-06, modified on 2017-05-12

Fractional Spin‐Labeling of Polymers for Enhancing NMR Sensitivity by Solvent‐Free Dynamic Nuclear Polarization

Keywords: cross polarization ; dynamic nuclear polarization ; magic angle spinning ; NMR spectroscopy ; peptides ; Range Structural Restraints ; Solid-State Nmr ; Proteins ; Spectroscopy Reference EPFL-ARTICLE-170435doi:10.1002/cphc.201100630View record in Web of Science Record created on 2011-11-29, modified on 2017-05-12

Functionalized pyrrolidine inhibitors of human type II α-mannosidases as anti-cancer agents: Optimizing the fit to the active site

Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi alpha-mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of alpha-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.

An Efficient Combinatorial Method for the Discovery of Glycosidase Inhibitors

Keywords: alpha-mannosidase inhibitor ; advanced malignancies ; swainsonine ; glycosylation ; chemistry ; libraries ; analogs Reference LGSA-ARTICLE-2002-011doi:10.1002/1439-7633(20020503)3:5 3.0.CO;2-DView record in Web of Science Record created on 2005-11-09, modified on 2017-05-12

Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products

Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect.

Evaluation of docking programs for predicting binding of Golgi alpha-mannosidase II inhibitors: a comparison with crystallography

Golgi α‐mannosidase II (GMII), a zinc‐dependent glycosyl hydrolase, is a promising target for drug development in anti‐tumor therapies. Using X‐ray crystallography, we have determined the structure of Drosophila melanogaster GMII (dGMII) complexed with three different inhibitors exhibiting IC50s ranging from 80 to 1000 μM. These structures, along with those of seven other available dGMII/inhibitor complexes, were then used as a basis for the evaluation of seven docking programs (GOLD, Glide, FlexX, AutoDock, eHiTS, LigandFit, and FITTED). We found that small inhibitors could be accurately docked by most of the software, while docking of larger compounds (i.e., those with extended aromatic cycles or long aliphatic chains) was more problematic. Overall, Glide provided the best docking results, with the most accurately predicted binding around the active site zinc atom. Further evaluation of Glides performance revealed its ability to extract active compounds from a benchmark library of decoys. Proteins 2007.

A short and convenient synthesis of 1-deoxymannojirimycin and N-oxy analogues from D-fructose.

Ketonitrone 8 was prepared from D-fructose as an inexpensive starting material and was used in a stereoselective synthesis of 1-deoxymannojirimycin (DMJ, 4), of its previously unknown N-hydroxy analogue 15, and of the polyhydroxylated ketonitrone 14. The latter were assayed as potential glycosidase inhibitors on a panel of 13 selected purified enzymes. Disappointingly, the polyhydroxylated nitrone 14 inhibited none of these enzymes. However, N-hydroxy-DMJ (15) exhibited a moderate and non-selective activity toward the snail beta-mannosidase EC 3.2.1.25.