Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors
文献类型：期刊论文
| 作者 | Long, Ya-Qiu4; Huang, Shao-Xu4; Zawahir, Zahrah2; Xu, Zhong-Liang4; Li, Huiyuan4; Sanchez, Tino W.2; Zhi, Ying4; De Houwer, Stephanie1,3; Christ, Frauke1,3; Debyser, Zeger1,3 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013-07-11 |
| 卷号 | 56期号:13页码:5601-5612 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm4006516 |
| 文献子类 | Article |
| 英文摘要 | HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome involving several interactions with the viral and cellular proteins. We have previously identified peptide IN inhibitors derived from the a-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon stapling of these peptides to stabilize their., helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture. Furthermore, the stabilized peptides inhibit the interaction of IN with the cellular cofactor LEDGF/p75. Cellular uptake of the stapled peptide was confirmed in four different cell lines using a fluorescein-labeled analogue. Given their enhanced potency and cell permeability, these stapled peptides can serve as not only lead IN inhibitors but also prototypical biochemical probes or "nanoneedles" for the elucidation of HIV-1 IN dimerization and host cofactor interactions within their native cellular environment. |
| WOS关键词 | ALPHA-AMINO-ACIDS ; LEDGF/P75 PROTEIN ; P53 PEPTIDE ; SIDE-CHAIN ; BH3 HELIX ; IN-VIVO ; DOLUTEGRAVIR ; REPLICATION ; DISCOVERY ; INFECTION |
| 资助项目 | National Natural Science Foundation of China[81021062] ; National Natural Science Foundation of China[81072527] ; National Natural Science Foundation of China[81123004] ; Science and Technology Commission of Shanghai Municipality[08JC1422200] ; NIH/NIAID[R21AI081610] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000321884200028 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277541]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Long, Ya-Qiu |
| 作者单位 | 1.Katholieke Univ Leuven, Lab Mol Virol & Gene Therapy, B-3000 Louvain, Belgium; 2.Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90033 USA; 3.IRC KUIAK, B-3000 Louvain, Belgium 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Long, Ya-Qiu,Huang, Shao-Xu,Zawahir, Zahrah,et al. Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(13):5601-5612. |
| APA | Long, Ya-Qiu.,Huang, Shao-Xu.,Zawahir, Zahrah.,Xu, Zhong-Liang.,Li, Huiyuan.,...&Neamati, Noun.(2013).Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,56(13),5601-5612. |
| MLA | Long, Ya-Qiu,et al."Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 56.13(2013):5601-5612. |
入库方式： OAI收割
来源：上海药物研究所
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