Acyclic Tethers Mimicking Subunits of Polysaccharide Ligands: Selectin Antagonists

Calosso, Mickael; Tambutet, Guillaume; Charpentier, Daniel; St‐Pierre, Gabrielle; Vaillancourt, Marc; Bencheqroun, Mohammed; Gratton, Jean‐Philippe; Prévost, Michel; Guindon, Yvan

doi:10.1021/ml500266x

Cited by 9 publications

(19 citation statements)

References 39 publications

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“…The experimentally confirmed inhibitors published in the articles by Calosso et al. (2014) ) and Gouge-Ibert et al.…”

Section: Resultssupporting

confidence: 52%

“…Nonetheless, while IC 50 values allow for a straightforward comparison of the inhibitors within a single study, they cannot be used to compare inhibitors among the different studies due to the various experimental conditions. To deal with this issue, the logarithm of the ratio of IC 50 of a compound to IC 50 of sLe x was used ( Calosso et al. 2014 ) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}\begin{equation*} \log \left(\mathrm{ratio}\right)=\log \left(\frac{IC_{50,{\mathrm{sLe}}^{\mathrm{X}}}}{IC_{50,\mathrm{cpd}}}\right).…”

Section: Resultsmentioning

confidence: 99%

“…To demonstrate the rigid receptor issue, docking of compounds 3 and 26 from the paper by Calosso et al. (2014) ) will be discussed in more detail.…”

Section: Resultsmentioning

confidence: 99%

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Pan-selectin inhibitors as potential therapeutics for COVID-19 treatment: in silico screening study

et al. 2021

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Coronavirus disease 2019 (COVID-19) has spread rapidly throughout the globe. The spectrum of disease is broad but among hospitalized patients with COVID-19, respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. There is an urgent need for an effective treatment. The current focus has been developing novel therapeutics, including antivirals, protease inhibitors, vaccines, and targeting the overactive cytokine response with anti-cytokine therapy. The overproduction of early response proinflammatory cytokines results in what has been described as a “cytokine storm” is leading eventually to death when the cells fail to terminate the inflammatory response. Accumulating evidence shows that inflammatory cytokines induce selectin ligands that play a crucial role in the pathogenesis of inflammatory diseases by mediating leukocyte migration from the blood into the tissue. Thus, the selectins and selectin ligands represent a promising therapeutic target for the treatment of COVID-19. In this paper, potential pan-selectin inhibitors were identified employing a virtual screening using a docking procedure. For this purpose, the Asinex and ZINC databases of ligands, including approved drugs, biogenic compounds, and glycomimetics, altogether 923 602 compounds, were screened against the P-, L-, and E-selectin. At first, the experimentally confirmed inhibitors were docked into all three selectins' carbohydrate recognition domains to assess the suitability of the screening procedure. Finally, based on the evaluation of ligands binding, we propose ten purchasable pan-selectin inhibitors to develop COVID-19 therapeutics.

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“…The experimentally confirmed inhibitors published in the articles by Calosso et al. (2014) ) and Gouge-Ibert et al.…”

Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

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Pan-selectin inhibitors as potential therapeutics for COVID-19 treatment: in silico screening study

et al. 2021

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“…Similarly, it was shown that sialic acid had little effect on the binding to E-selectin [48,343]. Thus, it was suggested to replace the GlcNAc residue with an acyclic tether with defined conformational bias [344], which led to the design and synthesis of selectin antagonists that exhibited the required activity both in vitro and in vivo [345]. Recently, several E-selectin inhibitors that have potential for anti-inflammatory drug development were designed with an approach that targets neighboring regions of the binding site [346].…”

Section: Glycomimetic Inhibitorsmentioning

confidence: 99%

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

2020

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Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLex is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLex tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde’s two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.

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“…Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-α-d-mannopyranoside (4) Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-α-d-mannopyranoside (4) was synthesized following a slightly modified protocol reported by Calosso M. et al [43].…”

Section: Chemical Synthesis Of Monosaccharides 2-9mentioning

confidence: 99%

Developing a Library of Mannose-Based Mono- and Disaccharides: A General Chemoenzymatic Approach to Monohydroxylated Building Blocks

et al. 2020

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Regioselective deprotection of acetylated mannose-based mono- and disaccharides differently functionalized in anomeric position was achieved by enzymatic hydrolysis. Candida rugosa lipase (CRL) and Bacillus pumilus acetyl xylan esterase (AXE) were immobilized on octyl-Sepharose and glyoxyl-agarose, respectively. The regioselectivity of the biocatalysts was affected by the sugar structure and functionalization in anomeric position. Generally, CRL was able to catalyze regioselective deprotection of acetylated monosaccharides in C6 position. When acetylated disaccharides were used as substrates, AXE exhibited a marked preference for the C2, or C6 position when C2 was involved in the glycosidic bond. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monohydroxylated building blocks that could be used as intermediates for the synthesis of mannosylated glycoconjugate vaccines targeting mannose receptors of antigen presenting cells.

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Acyclic Tethers Mimicking Subunits of Polysaccharide Ligands: Selectin Antagonists

Cited by 9 publications

References 39 publications

Pan-selectin inhibitors as potential therapeutics for COVID-19 treatment: in silico screening study

Pan-selectin inhibitors as potential therapeutics for COVID-19 treatment: in silico screening study

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

Developing a Library of Mannose-Based Mono- and Disaccharides: A General Chemoenzymatic Approach to Monohydroxylated Building Blocks

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