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8 results on '"GLYCOPROTEIN LIGAND"'

4. A benzoboroxole-based affinity ligand for glycoprotein purification at physiological pH.

Author

Rowe, Laura, El Khoury, Graziella, and Lowe, Christopher R.

Abstract

Developing ligands capable of carbohydrate recognition has become increasingly important as the essential roles of glycoproteins and glycolipids in a diverse array of cellular signaling, pathophysiology, and immune response mechanisms are elucidated. Effective ligands for the glycan portion of glycoproteins and glycolipids are needed for pre-enrichment proteomics strategies, as well as for the purification of individual glycoproteins from complex biological milieu encountered both in biochemistry research and bio-pharmaceutical development. In this work, we developed a carbohydrate specific affinity ligand for glycoprotein purification using a one-pot, multi-component synthesis reaction (Ugi synthesis) and an amine-functionalized benzoboroxole moiety immobilized on agarose beads. Benzoboroxoles are unique boronic acid derivatives that have recently been found to bind specifically to the cis-diol groups of carbohydrates at physiological pH, with superior affinity to any other Wulff-type boronic acid. The solid-phase affinity ligand developed herein specifically binds the carbohydrate moiety of the glycoprotein glucose oxidase, as well as a fluorescein isothiocyanate-dextran, as shown through deglycosylation binding studies. Additionally, the ligand is able to purify glucose oxidase from crude Escherichia coli lysate, at physiological pH, equitably to commercially available boronic acid-functionalized agarose beads that required alkaline pH conditions. Thus, this affinity ligand is a marked improvement on current, commercially available boronic acid-based glycoprotein enrichment matrices and has the potential to exhibit high individual glycoprotein specificity because of the additional functional groups available for variation on the Ugi scaffold. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2016
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6. E-selectin ligands recognised by HECA452 induce drug resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271

Author

Shaji Kumar, Elena Ellert, M. Andrulis, C. Connolly, W. E. Fogler, Lucy Kirkham-McCarthy, S. C. Locatelli-Hoops, Alessandro Natoni, Cian McEllistrim, I. Oliva, Niamh Keane, T. A.G. Smith, Michael O'Dwyer, Marc-Steffen Raab, Alokkumar Jha, Siobhan Glavey, and John L. Magnani

Subjects
0301 basic medicine, Cancer Research, Pharmacology, Ligands, in-vivo, Bortezomib, Mice, 0302 clinical medicine, fucosyl-transferase, Recurrence, Tumor Cells, Cultured, fuct-vii, Receptor, Multiple myeloma, t-cells, biology, Hematology, Prognosis, glycoprotein ligand, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Original Article, Female, E-Selectin, Multiple Myeloma, E-selectin Antagonist GMI-1271, medicine.drug, Protein Binding, Cell Survival, p-selectin, 03 medical and health sciences, In vivo, E-selectin, medicine, sialyl le(x), Cell Adhesion, Animals, Gene Expression Profiling, bone-marrow microenvironment, leukocyte adhesion, medicine.disease, Xenograft Model Antitumor Assays, In vitro, Disease Models, Animal, 030104 developmental biology, multiple-myeloma, Drug Resistance, Neoplasm, Cancer research, biology.protein, Bone marrow
Abstract

Multiple myeloma (MM) is characterized by the clonal expansion and metastatic spread of malignant plasma cells to multiple sites in the bone marrow (BM). Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the generation of E-selectin ligands, in MM BM homing and resistance to therapy. Since E-selectin is constitutively expressed in the BM microvasculature, we wished to establish the contribution of E-selectin ligands to MM biology. We report that functional E-selectin ligands are restricted to a minor subpopulation of MM cell lines which, upon expansion, demonstrate specific and robust interaction with recombinant E-selectin in vitro. Moreover, an increase in the mRNA levels of genes involved in the generation of E-selectin ligands was associated with inferior progression-free survival in the CoMMpass study. In vivo, E-selectin ligand-enriched cells induced a more aggressive disease and were completely insensitive to Bortezomib. Importantly, this resistance could be reverted by co-administration of GMI-1271, a specific glycomimetic antagonist of E-selectin. Finally, we report that E-selectin ligand-bearing cells are present in primary MM samples from BM and peripheral blood with a higher proportion seen in relapsed patients. This study provides a rationale for targeting E-selectin receptor/ligand interactions to overcome MM metastasis and chemoresistance.

Published
2017

8. Soluble Siglec-5 associates to PSGL-1 and displays anti-inflammatory activity

Author

Pepin, Marion, Mezouar, Soraya, Pegon, Julie, Muczynski, Vincent, Adam, Frédéric, Bianchini, Elsa P, Bazaa, Amine, Proulle, Valerie, Rupin, Alain, Paysant, Jerome, Panicot-Dubois, Laurence, Christophe, Olivier D., Dubois, Christophe, Lenting, Peter J, Denis, Cécile V, Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Recherches Internationales Servier [Suresnes] (IRIS), The study was financially supported by a PhD-research grant from Institut Servier & Association Nationale de la Recherche Technique (Contrat CIFRE) to JPe, and an Inserm-Poste d’Accueil-grant (# ASC13101LSA) to MP., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Anti-Inflammatory Agents/pharmacology, E-SELECTIN LIGAND-1, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, MESH: Membrane Glycoproteins/genetics, MESH: Antigens, Differentiation, Myelomonocytic/metabolism, MESH: Lectins/metabolism, MESH: Antigens, CD/pharmacology, MESH: Leukocytes, Mononuclear/drug effects, Lectins, MESH: Animals, MYELOID CELLS, MESH: E-Selectin/metabolism, NEUTROPHILS, IN-VIVO, MESH: Inflammation/drug therapy, Membrane Glycoproteins, MESH: Inflammation/chemically induced, MESH: Inflammation/pathology, MESH: Membrane Glycoproteins/metabolism, MESH: Leukocyte Rolling/physiology, P-Selectin, Female, E-Selectin, MESH: Leukocytes, Mononuclear/metabolism, CD33-RELATED SIGLECS, VON-WILLEBRAND-FACTOR, MESH: Lectins/pharmacology, Antigens, Differentiation, Myelomonocytic, MESH: Antigens, Differentiation, Myelomonocytic/pharmacology, MESH: Tumor Necrosis Factor-alpha/toxicity, GLYCOPROTEIN LIGAND, MESH: Antigens, CD/metabolism, Article, MESH: Mice, Inbred C57BL, Antigens, CD, Animals, Humans, Leukocyte Rolling, Protein Interaction Domains and Motifs, MESH: Antigens, Differentiation, Myelomonocytic/genetics, SIALIC-ACID, Inflammation, MESH: Protein Interaction Domains and Motifs, MESH: Humans, Tumor Necrosis Factor-alpha, MESH: Lectins/genetics, MESH: Solubility, Mice, Inbred C57BL, Disease Models, Animal, Solubility, Leukocytes, Mononuclear, MESH: Antigens, CD/genetics, IMMUNE-SYSTEM, MESH: Disease Models, Animal, MESH: Female, MESH: P-Selectin/metabolism
Abstract

International audience; Interactions between endothelial selectins and the leukocyte counter-receptor PSGL1 mediates leukocyte recruitment to inflammation sites. PSGL1 is highly sialylated, making it a potential ligand for Siglec-5, a leukocyte-receptor that recognizes sialic acid structures. Binding assays using soluble Siglec-5 variants (sSiglec-5/C4BP and sSiglec-5/Fc) revealed a dose- and calcium-dependent binding to PSGL1. Pre-treatment of PSGL1 with sialidase reduced Siglec-5 binding by 79 ± 4%. In confocal immune-fluorescence assays, we observed that 50% of Peripheral Blood Mononuclear Cells (PBMCs) simultaneously express PSGL1 and Siglec-5. Duolink-proximity ligation analysis demonstrated that PSGL1 and Siglec-5 are in close proximity (

Published
2016
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