The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Philippe Compain - One of the best experts on this subject based on the ideXlab platform.
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Iminosugars as a new class of cholinesterase inhibitors.
Bioorganic and Medicinal Chemistry Letters, 2015Co-Authors: Camille Decroocq, Fabien Stauffert, Olivier Pamlard, Farah Oulaïdi, Estelle Gallienne, Olivier R Martin, Catherine Guillou, Philippe CompainAbstract:To further extend the scope of iminosugar biological activity, a systematic structure-activity relationship investigation has been performed by synthesizing and evaluating as cholinesterase inhibitors a library of twenty-three iminoalditols with different substitutions and stereochemistry patterns. These compounds have been evaluated in vitro for the inhibition of cholinesterases (different sources of acetylcholinesterase and butyrylcholinesterase). Some compounds have IC50 values in the micromolar range and display significant inhibition selectivity for butyrylcholinesterase over acetylcholinesterase. These are the first examples of iminosugar-based inhibitors of cholinesterases.
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A Convergent Strategy for the Synthesis of Second-Generation Iminosugar Clusters Using “Clickable” Trivalent Dendrons
European Journal of Organic Chemistry, 2014Co-Authors: Antoine Joosten, Jérémy Schneider, Mathieu Lepage, Celine Tarnus, Anne Bodlenner, Philippe CompainAbstract:A convergent strategy to access high‐valency iminosugar clusters based on two successive CuI‐catalysed azide–alkyne cycloadditions is reported. The key step of this approach relies on the grafting of azide‐armed trivalent iminosugar dendrons onto polyalkyne “clickable” scaffolds, thus tripling their initial valency. As a proof of concept, the synthesis of cyclodextrin‐based clusters containing the highest number of peripheral iminosugar ligands reported to date has been achieved. Evaluation of these compounds as mannosidase inhibitors revealed one of the strongest multivalent effects observed so far in glycosidase inhibition.
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The multivalent effect in glycosidase inhibition: probing the influence of valency, peripheral ligand structure, and topology with cyclodextrin-based iminosugar click clusters.
ChemBioChem, 2013Co-Authors: Camille Decroocq, Raphaël Sergent, Teresa Mena Barragán, Carmen Ortiz Mellet, Antoine Joosten, Philippe CompainAbstract:: In view of recent reports of a strong multivalent effect in glycosidase inhibition, a library of β-CD-based multivalent iminosugars has been efficiently synthesized by way of Cu(I) -catalyzed azide-alkyne cycloaddition (CuAAC). In combination with the first application of isothermal titration calorimetry (ITC) experiments to the study of multivalent iminosugar-enzyme interactions, the inhibition properties of these click clusters were evaluated on a panel of glycosidases. The structural parameters that were varied include valency, peripheral ligand structure, and topology. The inhibition results obtained with the iminosugar clusters further highlight the importance of multivalency in the inhibition of α-mannosidase. Generally, the evaluated multivalent iminosugars displayed comparable thermodynamic signatures of binding towards α-mannosidase (Jack bean): that is, large negative enthalpies of complexation coupled with small entropies of either sign. In addition, the enthalpy-entropy compensation observed in all tested cases may be attributed to a common mechanism of dissociation for the enzyme-multivalent iminosugar interactions. The measured binding stoichiometries indicated that each iminosugar cluster interacts with no more than one protein molecule.
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tactics and strategies for the synthesis of iminosugar c glycosides a review
Tetrahedron-asymmetry, 2009Co-Authors: Philippe Compain, Vincent Chagnault, Olivier R MartinAbstract:Three decades after their first synthesis, iminosugar C-glycosides have become an important class of iminosugars with promising biological and therapeutic properties. The purpose of this review is to provide an overview of the versatile strategies that have been developed to synthesize this family of stable imino-analogues of glycosides and glycoconjugates. Some guidelines and predictive stereoselective models are presented to facilitate the design of synthetic strategies toward iminosugar C-glycosides of defined configuration.
Olivier R Martin - One of the best experts on this subject based on the ideXlab platform.
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Iminosugars as a new class of cholinesterase inhibitors.
Bioorganic and Medicinal Chemistry Letters, 2015Co-Authors: Camille Decroocq, Fabien Stauffert, Olivier Pamlard, Farah Oulaïdi, Estelle Gallienne, Olivier R Martin, Catherine Guillou, Philippe CompainAbstract:To further extend the scope of iminosugar biological activity, a systematic structure-activity relationship investigation has been performed by synthesizing and evaluating as cholinesterase inhibitors a library of twenty-three iminoalditols with different substitutions and stereochemistry patterns. These compounds have been evaluated in vitro for the inhibition of cholinesterases (different sources of acetylcholinesterase and butyrylcholinesterase). Some compounds have IC50 values in the micromolar range and display significant inhibition selectivity for butyrylcholinesterase over acetylcholinesterase. These are the first examples of iminosugar-based inhibitors of cholinesterases.
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tactics and strategies for the synthesis of iminosugar c glycosides a review
Tetrahedron-asymmetry, 2009Co-Authors: Philippe Compain, Vincent Chagnault, Olivier R MartinAbstract:Three decades after their first synthesis, iminosugar C-glycosides have become an important class of iminosugars with promising biological and therapeutic properties. The purpose of this review is to provide an overview of the versatile strategies that have been developed to synthesize this family of stable imino-analogues of glycosides and glycoconjugates. Some guidelines and predictive stereoselective models are presented to facilitate the design of synthetic strategies toward iminosugar C-glycosides of defined configuration.
Chihuey Wong - One of the best experts on this subject based on the ideXlab platform.
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towards new antibiotics targeting bacterial transglycosylase synthesis of a lipid ii analog as stable transition state mimic inhibitor
Bioorganic & Medicinal Chemistry Letters, 2018Co-Authors: Xiaolei Wang, Larissa B Krasnova, Tingjen Cheng, Chihuey WongAbstract:Abstract Described here is the asymmetric synthesis of iminosugar 2b, a Lipid II analog, designed to mimic the transition state of transglycosylation catalyzed by the bacterial transglycosylase. The high density of functional groups, together with a rich stereochemistry, represents an extraordinary challenge for chemical synthesis. The key 2,6-anti- stereochemistry of the iminosugar ring was established through an iridium-catalyzed asymmetric allylic amination. The developed synthetic route is suitable for the synthesis of focused libraries to enable the structure–activity relationship study and late-stage modification of iminosugar scaffold with variable lipid, peptide and sugar substituents. Compound 2b showed 70% inhibition of transglycosylase from Acinetobacter baumannii, providing a basis for further improvement.
Masahiro Hirama - One of the best experts on this subject based on the ideXlab platform.
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Practical Synthesis of theC-1027 Aminosugar Moiety
Synlett, 2010Co-Authors: Keiichiro Hirai, Yukio Tamura, Itaru Sato, Masahiro HiramaAbstract:A concise and reliable synthetic route to the Aminosugar moiety of the C-1027 chromophore was developed. The Aminosugar moiety was synthesized from L-glutamic acid in 11 steps and 13% overall yield.
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Synthesis and absolute stereochemistry of the Aminosugar moiety of antibiotic C-1027 chromophore
Tetrahedron Letters, 1993Co-Authors: Kyo-ichiro Iida, Masahiro Hirama, Takaaki Ishii, Toshio Otani, Yoshinori Minami, Ken-ichiro YoshidaAbstract:Abstract Stereocontrolled synthesis and absolute stereochemistry of the Aminosugar moiety of C-1027 chromophore have been disclosed.
Catherine F Yang - One of the best experts on this subject based on the ideXlab platform.
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the neocarzinostatin biosynthetic gene cluster from streptomyces carzinostaticus atcc 15944 involving two iterative type i polyketide synthases
Chemistry & Biology, 2005Co-Authors: Wen Liu, Koichi Nonaka, Liping Nie, Jian Zhang, Steven D Christenson, Juyun Bae, Steven G Van Lanen, Emmanuel Zazopoulos, Chris M Farnet, Catherine F YangAbstract:The biosynthetic gene cluster for the enediyne antitumor antibiotic neocarzinostatin (NCS) was localized to 130 kb continuous DNA from Streptomyces carzinostaticus ATCC15944 and confirmed by gene inactivation. DNA sequence analysis of 92 kb of the cloned region revealed 68 open reading frames (ORFs), 47 of which were determined to constitute the NCS cluster. Sequence analysis of the genes within the NCS cluster suggested dNDP-D-mannose as a precursor for the deoxy Aminosugar, revealed two distinct type I polyketide synthases (PKSs), and supported a convergent model for NCS chromophore biosynthesis from the deoxy Aminosugar, naphthoic acid, and enediyne core building blocks. These findings shed light into deoxysugar biosynthesis, further support the iterative type I PKS paradigm for enediyne core biosynthesis, and unveil a mechanism for microbial polycyclic aromatic polyketide biosynthesis by an iterative type I PKS.