Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation

doi:10.3892/ol.2014.1887

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation
	Kawashima, Nagako 1; Qu, Huanhuan 2,4; Lobaton, Marlin 1; Zhu, Zhenyuan 2; Sollogoub, Matthieu 2; Cavenee, Webster K.3; Handa, Kazuko 1; Hakomori, Sen-Itiroh 1,5,6; Zhang, Yongmin 2,7
刊名	ONCOLOGY LETTERS
	2014-04
卷号	7 期号:4 页码:933-940
关键词	EGFR inhibitors cell proliferation EGFR activation GM3 glycosphingolipids chloro-derivatives of GM3
ISSN号	1792-1074
DOI	10.3892/ol.2014.1887
文献子类	Article
英文摘要	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 ([H-3]-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 Delta EGFR, 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 Delta EGFR.
资助项目	Universite Pierre et Marie Curie-Paris 6 for the program of LIA[00000000] ; Biomembrane Institute[00000000] ; China Scholarship Council[00000000] ; [P01-CA95616]
WOS关键词	GANGLIOSIDE-MEDIATED MODULATION ; TYROSINE PHOSPHORYLATION ; CELL-GROWTH ; HUMAN GLIOBLASTOMAS ; CANCER-CELLS ; GM3 ; GLYCOSYLATION ; CONVERSION ; BINDING ; KINASE
WOS研究方向	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000334311900003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277140]
专题	药理学第三研究室
通讯作者	Hakomori, Sen-Itiroh
作者单位	1.Pacific Northwest Res Inst, Div Biomembrane Res, Seattle, WA 98122 USA; 2.Univ Paris 06, Inst Paris Mol Chem, F-75005 Paris, France; 3.Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 201203, Peoples R China; 5.Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA; 6.Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA; 7.Jianghan Univ, Inst Interdisciplinary Res, Wuhan Econ & Technol Dev Zone, Wuhan 430056, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Kawashima, Nagako,Qu, Huanhuan,Lobaton, Marlin,et al. Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation[J]. ONCOLOGY LETTERS,2014,7(4):933-940.
APA	Kawashima, Nagako.,Qu, Huanhuan.,Lobaton, Marlin.,Zhu, Zhenyuan.,Sollogoub, Matthieu.,...&Zhang, Yongmin.(2014).Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation.ONCOLOGY LETTERS,7(4),933-940.
MLA	Kawashima, Nagako,et al."Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation".ONCOLOGY LETTERS 7.4(2014):933-940.