Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface
文献类型：期刊论文
| 作者 | Rashad, Adel A.1; Song, Li-Rui2,3,5; Holmes, Andrew P.1; Acharya, Kriti1; Zhang, Shiyu1,4; Wang, Zhi-Long2; Gary, Ebony7; Xie, Xin2 ; Pirrone, Vanessa6; Kutzler, Michele A.7
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2018-06-14 |
| 卷号 | 61期号:11页码:5020-5033 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.8b00477 |
| 文献子类 | Article |
| 英文摘要 | To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of the HIV-1 envelope (Env) gp120 protein and the host-cell coreceptor (CoR) protein can be covalently joined into bifunctional synergistic combinations with improved antiviral capabilities. A synthetic protocol was established to covalently combine a CCR5 small-molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components and, at the same time, exhibited low to subnanomolar potencies in inhibiting cell infection by different pseudoviruses, which were substantially greater than those of a noncovalent mixture of the individual components. The results demonstrate that targeting the virus cell interface with a single molecule can result in improved potencies and also the introduction of new phenotypes to the chimeric inhibitor, such as the irreversible inactivation of HIV-1. |
| WOS关键词 | ENV GP120 ; MARAVIROC UK-427,857 ; FUSION-INHIBITOR ; ENTRY INHIBITOR ; HIV-1 GP120 ; IN-VITRO ; STRUCTURAL DETERMINANTS ; DUAL ANTAGONIST ; PEPTIDE ; BINDING |
| 资助项目 | National Natural Science Foundation of China[81761128022] ; National Natural Science Foundation of China[81361120410] ; National Natural Science Foundation of China[81325020] ; National Institutes of Health[R01AI106633] ; National Institutes of Health[P01GMS6550] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000435613100024 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279706]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Long, Ya-Qiu; Chaiken, Irwin |
| 作者单位 | 1.Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19102 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.Soochow Univ, Med Coll, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China; 4.Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA 5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 6.Drexel Univ, Dept Microbiol & Immunol, Coll Med, Philadelphia, PA 19102 USA; 7.Drexel Univ, Dept Med, Coll Med, Philadelphia, PA 19102 USA; |
| 推荐引用方式 GB/T 7714 | Rashad, Adel A.,Song, Li-Rui,Holmes, Andrew P.,et al. Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface[J]. JOURNAL OF MEDICINAL CHEMISTRY,2018,61(11):5020-5033. |
| APA | Rashad, Adel A..,Song, Li-Rui.,Holmes, Andrew P..,Acharya, Kriti.,Zhang, Shiyu.,...&Chaiken, Irwin.(2018).Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface.JOURNAL OF MEDICINAL CHEMISTRY,61(11),5020-5033. |
| MLA | Rashad, Adel A.,et al."Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface".JOURNAL OF MEDICINAL CHEMISTRY 61.11(2018):5020-5033. |
入库方式： OAI收割
来源：上海药物研究所
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