Multiple and multivalent interactions of novel anti-AIDS drug candidates, sulfated polymannuronate (SPMG)-derived oligosaccharides, with gp120 and their anti-HIV activities
文献类型：期刊论文
| 作者 | Liu, HY; Geng, MY ; Xin, XL; Li, FC; Zhang, ZQ; Li, J; Ding, J
|
| 刊名 | GLYCOBIOLOGY
 |
| 出版日期 | 2005-05 |
| 卷号 | 15期号:5页码:501-510 |
| 关键词 | anti-HIV-IIIB activity rgp120 SPMG-derived oligosaccharide sulfated polymannuronate surface plasmon resonance |
| ISSN号 | 0959-6658 |
| DOI | 10.1093/glycob/cwi031 |
| 文献子类 | Article |
| 英文摘要 | Sulfated polymannuronate (SPMG), a novel anti-AIDS drug candidate, combats HIV-1 infection mainly by binding to gp120 protein with high affinity. To explore the structural basis of this anti-HIV-1 action, size-defined oligosaccharides were prepared by semi-synthesis or separated from native SPMG. In this study, a series of homogeneously sized SPMG fragments are evaluated for their capacity to bind rgp120 using surface plasmon resonance (SPR) analysis. The minimum SPMG fragment size that interacts with rgp120 is a hexasaccharide. Additionally, binding capacity increases with the molecular size of oligosaccharides, with the affinity of large fragments (>= 15-16 saccharides) approaching that of full-sized SPMG. Competitive inhibition and stoichiometric analyses disclose that SPMG oligos bind to multiple binding sites on gp120. Sugar chains longer than 15-16 saccharide residues (SPMG) display multivalent interactions, with one sugar chain binding to two or three gp120 molecules. Consistent with binding data, a positive correlation exists between the size of SPMG oligosaccharides and their anti-HIV activity. The octasaccharide is established to be the minimal active fragment inhibiting syncytium formation and lowering the P-24 core antigen level in HIV-IIIB-infected CEM cells. Alternatively, about 50% anti-HIV activity was observed for 15-16 saccharides, whereas a 19-20-saccharide fragment displayed anti-HIV activity equivalent to native SPMG. The structures of the unique minimum hexasaccharide specifically recognized by gp120 and the minimum octasaccharide combating HIV-IIIB infection were representatively structured as [ManA (2s)beta 1-4 ManA(2s/3s)](n). |
| WOS关键词 | FIBROBLAST-GROWTH-FACTOR ; IN-VITRO ; ENVELOPE GLYCOPROTEIN ; ANTI-HIV-1 ACTIVITY ; TYPE-1 ; HEPARIN ; BINDING ; RECEPTOR ; GP41 ; V3 |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000228780000007 |
| 出版者 | OXFORD UNIV PRESS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273877]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Geng, MY |
| 作者单位 | 1.Ocean Univ China, Marine Drug & Food Inst, Dept Pharmacol, Qingdao 266003, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Div Antitumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, HY,Geng, MY,Xin, XL,et al. Multiple and multivalent interactions of novel anti-AIDS drug candidates, sulfated polymannuronate (SPMG)-derived oligosaccharides, with gp120 and their anti-HIV activities[J]. GLYCOBIOLOGY,2005,15(5):501-510. |
| APA | Liu, HY.,Geng, MY.,Xin, XL.,Li, FC.,Zhang, ZQ.,...&Ding, J.(2005).Multiple and multivalent interactions of novel anti-AIDS drug candidates, sulfated polymannuronate (SPMG)-derived oligosaccharides, with gp120 and their anti-HIV activities.GLYCOBIOLOGY,15(5),501-510. |
| MLA | Liu, HY,et al."Multiple and multivalent interactions of novel anti-AIDS drug candidates, sulfated polymannuronate (SPMG)-derived oligosaccharides, with gp120 and their anti-HIV activities".GLYCOBIOLOGY 15.5(2005):501-510. |
入库方式： OAI收割
来源：上海药物研究所
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