Structure-activity relationship study of WSS25 derivatives with anti-angiogenesis effects

doi:10.1007/s10719-012-9424-z

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

	Structure-activity relationship study of WSS25 derivatives with anti-angiogenesis effects
	Chen, Xia; Xiao, Fei; Wang, Ying; Fang, Jianping; Ding, Kan
刊名	GLYCOCONJUGATE JOURNAL
	2012-08
卷号	29 期号:5-6 页码:389-398
关键词	Gastrodia elata Sulfated polysaccharide derivative Anti-angiogenesis WSS25
ISSN号	0282-0080
DOI	10.1007/s10719-012-9424-z
文献子类	Article
英文摘要	WGEW, an alpha(1-4) linked glucan with an alpha(1-4) linked branch attached to C-6, was isolated from the rhizoma of Gastrodia elata Bl. WSS25, a sulfated derivative of WGEW, was reported to inhibit angiogenesis by disrupting BMP2/Smad/Id1 signaling pathway. However, the structure-activity relationship (SAR) for WSS25 is not known. To study the SAR, seven sulfated saccharides derived from WGEW degradation products, six sulfated polysaccharides with varying degrees of substitution, and four aminopropylated, carboxymethylated, phosphorylated, and acetylated derivatives of WGEW were prepared. A sulfated, unbranched product of polysaccharide was also obtained. The structural features of these derivatives were characterized by infrared spectroscopy and nuclear magnetic resonance spectroscopy. An HMEC-1 cell tube formation assay was employed to measure the antiangiogenic effect of the derivatives. The results indicated that only sulfated polysaccharides with molecular weights of more than 41,000 Da could inhibit HMEC-1 cell tube formation. The inhibition effect was dependent on the presence of a sulfate group, since the tube formation was not blocked by aminopropylated, carboxymethylated, phosphorylated, or acetylated WGEW. A higher degree of sulfate substitution on the polysaccharide led to a stronger inhibitory effect, and the degree of sulfate substitution between 0.173 and 0.194 was found to be optimal. Interestingly, the WGEW side chain was not required for anti-tube formation activity. All these preliminary results may provide a clue for further modification of the core structure of WSS25 to discover polysaccharide derivatives as novel anti-angiogenic inhibitors.
资助项目	New Drug Creation and Manufacturing Program[2012ZX09301001-003] ; National Science Fund for Distinguished Young Scholars[81125025] ; funds for Industry-University-Research Institution Alliance in Guangdong Province, China[2010A090200041]
WOS关键词	BONE MORPHOGENETIC PROTEIN ; HEPARAN-SULFATE ; TUMOR ANGIOGENESIS ; GANODERMA-LUCIDUM ; MOLECULAR-WEIGHT ; IN-VITRO ; GROWTH ; POLYSACCHARIDES ; CELLS ; DEGRADATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000307763900016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277999]
专题	药理学第三研究室
通讯作者	Fang, Jianping
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Xia,Xiao, Fei,Wang, Ying,et al. Structure-activity relationship study of WSS25 derivatives with anti-angiogenesis effects[J]. GLYCOCONJUGATE JOURNAL,2012,29(5-6):389-398.
APA	Chen, Xia,Xiao, Fei,Wang, Ying,Fang, Jianping,&Ding, Kan.(2012).Structure-activity relationship study of WSS25 derivatives with anti-angiogenesis effects.GLYCOCONJUGATE JOURNAL,29(5-6),389-398.
MLA	Chen, Xia,et al."Structure-activity relationship study of WSS25 derivatives with anti-angiogenesis effects".GLYCOCONJUGATE JOURNAL 29.5-6(2012):389-398.