Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation
| Autor: | Nagako Kawashima, Yongmin Zhang, Matthieu Sollogoub, S Hakomori, Kazuko Handa, Huanhuan Qu, Webster K. Cavenee, Marlin Lobaton, Zhenyuan Zhu |
|---|---|
| Přispěvatelé: | Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Shanghai Institute of Materia Medica, Glycochimie Organique Biologique et Supramoléculaire (GOBS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Ludwig Institute for Cancer Research, University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), University of Washington [Seattle], Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of California-University of California |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
GM3
Cancer Research Motility EGFR activation [CHIM]Chemical Sciences Epidermal growth factor receptor ComputingMilieux_MISCELLANEOUS EGFR inhibitors chloro-derivatives of GM3 glycosphingolipids biology Cell growth Autophosphorylation Articles Cell cycle 3. Good health Cell biology carbohydrates (lipids) cell proliferation Oncology Epidermoid carcinoma Immunology biology.protein lipids (amino acids peptides and proteins) A431 cells |
| Zdroj: | Oncology Letters Oncology Letters, 2014, 7 (4), pp.933--940. ⟨10.3892/ol.2014.1887⟩ Oncology Letters, Spandidos Publications, 2014, 7 (4), pp.933--940. ⟨10.3892/ol.2014.1887⟩ |
| ISSN: | 1792-1074 1792-1082 |
| DOI: | 10.3892/ol.2014.1887⟩ |
| Popis: | Glycosphingolipids are components of essentially all mammalian cell membranes and are involved in a variety of significant cellular functions, including proliferation, adhesion, motility and differentiation. Sialosyllactosylceramide (GM3) is known to inhibit the activation of epidermal growth factor receptor (EGFR). In the present study, an efficient method for the total chemical synthesis of monochloro- and dichloro-derivatives of the sialosyl residue of GM3 was developed. The structures of the synthesized compounds were fully characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In analyses of EGFR autophosphorylation and cell proliferation ([3H]-thymidine incorporation) in human epidermoid carcinoma A431 cells, two chloro-derivatives exhibited stronger inhibitory effects than GM3 on EGFR activity. Monochloro-GM3, but not GM3 or dichloro-GM3, showed a significant inhibitory effect on ΔEGFR, a splicing variant of EGFR that lacks exons 2–7 and is often found in human glioblastomas. The chemical synthesis of other GM3 derivatives using approaches similar to those described in the present study, has the potential to create more potent EGFR inhibitors to block cell growth or motility of a variety of types of cancer that express either wild-type EGFR or ΔEGFR. |
| Databáze: | OpenAIRE |
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