Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome (AIDS) drug candidate, targeting CD4 in lymphocytes
文献类型：期刊论文
| 作者 | Miao, BC; Geng, MY ; Li, J; Li, FC; Chen, HX; Guan, HS; Ding, J
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| 刊名 | BIOCHEMICAL PHARMACOLOGY
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| 出版日期 | 2004-08-15 |
| 卷号 | 68期号:4页码:641-649 |
| 关键词 | SPMG lymphocytes binding sites (receptors) CD4 FCM SPR |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2004.04.009 |
| 文献子类 | Article |
| 英文摘要 | Sulfated polymannuroguluronate (SPMG), a marine sulfated polysaccharide, has entered the Phase II clinical trial in China as the first anti-acquired immune deficiency syndrome (AIDS) drug candidate obtained from marine organisms. To determine the binding site(s) (receptors) of SPMG in lymphocytes mediating its anti-AIDS activities, fluorescein-5-isothiocyanate (FITC)-labeled SPMG was used to investigate SPMG binding to lymphocytes. Flow cytometry (FCM) and fluorescence microscopy analysis showed that the SPMG binds to lymphocytes in a rapid, specific, reversible, and saturable fashion. Several SPMG binding proteins were purified by affinity chromatography from lymphocyte membrane preparations. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis revealed that a 55 kDa lymphocyte membrane protein is CD4. To characterize the SPMG and CD4 interaction, inhibition assay and surface plasmon resonance (SPR) assay were carried out. SPMG bound to CD4 in a multivalent fashion with specificity. The binding of SPMG to human lymphocyte CD4 was competitively inhibited by human soluble CD4 (hsCD4). Likewise, the binding between hsCD4 and immobilized SPMG was blocked by excess free SPMG. These results indicate that CD4 is one of the specific SPMG binding sites (receptors) in lymphocytes. The interaction between SPMG and CD4 may provide a mechanistic explanation of the immunopotentiating and anti-AIDS activities of SPMG in human immunodeficiency virus (HINT) infected individuals. (C) 2004 Elsevier Inc. All rights reserved. |
| WOS关键词 | HIV-INFECTION ; ENTRY INHIBITORS ; BINDING-SITE ; DYE-BINDING ; CELL-FUSION ; RECEPTOR ; ACTIVATION ; POLYSACCHARIDES ; GLYCOPROTEIN ; PURIFICATION |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000223207800006 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274033]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Ding, J |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Div Antitumor Pharmacol, State Key Lab Drug Res,Shanghai Inst Materia Med, Shanghai, Peoples R China 2.Ocean Univ China, Dept Pharmacol, Marine Drug & Food Inst, Qingdao 266003, Peoples R China |
| 推荐引用方式 GB/T 7714 | Miao, BC,Geng, MY,Li, J,et al. Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome (AIDS) drug candidate, targeting CD4 in lymphocytes[J]. BIOCHEMICAL PHARMACOLOGY,2004,68(4):641-649. |
| APA | Miao, BC.,Geng, MY.,Li, J.,Li, FC.,Chen, HX.,...&Ding, J.(2004).Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome (AIDS) drug candidate, targeting CD4 in lymphocytes.BIOCHEMICAL PHARMACOLOGY,68(4),641-649. |
| MLA | Miao, BC,et al."Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome (AIDS) drug candidate, targeting CD4 in lymphocytes".BIOCHEMICAL PHARMACOLOGY 68.4(2004):641-649. |
入库方式： OAI收割
来源：上海药物研究所
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