Engineering a switch-on peptide to ricin A chain for increasing its specificity towards HIV-infected cells
文献类型：期刊论文
| 作者 | Au KY1; Wang RR2; Wong YT1; Wong KB1; Zheng YT[*]2; Shaw PC[*]1 |
| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA
 |
| 出版日期 | 2014 |
| 卷号 | 1840期号:3页码:958-963 |
| 关键词 | Ribosome-inactivating protein Ricin HIV Protease |
| 通讯作者 | zhengyt@mail.kiz.ac.cn ; pcshaw@cuhk.edu.hk |
| 合作状况 | 其它 |
| 英文摘要 | Background: Ricin is a type II ribosome-inactivating protein (RIP) that potently inactivates eukaryotic ribosomes by removing a specific adenine residue at the conserved alpha-sarcin/ricin loop of 28S ribosomal RNA (rRNA). Here, we try to increase the specificity of the enzymatically active ricin A chain (RTA) towards human immunodeficiency virus type 1 (HIV-1) by adding a loop with HIV protease recognition site to RTA. Methods: HIV-specific RTA variants were constructed by inserting a peptide with HIV-protease recognition site either internally or at the C-terminal region of wild type RTA Cleavability of variants by viral protease was tested in vitro and in HIV-infected cells. The production of viral p24 antigen and syncytium in the presence of C-terminal variants was measured to examine the anti-HIV activities of the variants. Results: C-terminal RTA variants were specifically cleaved by HIV-1 protease both in vitro and in HIV-infected cells. Upon proteolysis, the processed variants showed enhanced antiviral effect with low cytotoxicity towards uninfected cells. Conclusions: RTA variants with HIV protease recognition sequence engineered at the C-terminus were cleaved and the products mediated specific inhibitory effect towards HIV replication. General significance: Current cocktail treatment of HIV infection fails to eradicate the virus from patients. Here we illustrate the feasibility of targeting an RIP towards HIV-infected cells by incorporation of HIV protease cleavage sequence. This approach may be generalized to other RIPs and is promising in drug design for combating HIV. |
| 收录类别 | SCI |
| 资助信息 | Work in Hong Kong was supported by a grant from the Research Fund for the Control of Infectious Diseases (Project No. 10090452). Work in Kunming was supported by the Key Scientific and Technological Program of China (2012ZX10001-006; 2012ZX10001-007) and NSFC (81001462, 81102483). |
| 语种 | 英语 |
| WOS记录号 | WOS:000331344700004 |
| 公开日期 | 2014-04-04 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7833]  |
| 专题 | 昆明动物研究所_分子免疫药理学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Biochemistry Programme and Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China |
| 推荐引用方式 GB/T 7714 | Au KY,Wang RR,Wong YT,et al. Engineering a switch-on peptide to ricin A chain for increasing its specificity towards HIV-infected cells[J]. BIOCHIMICA ET BIOPHYSICA ACTA,2014,1840(3):958-963. |
| APA | Au KY,Wang RR,Wong YT,Wong KB,Zheng YT[*],&Shaw PC[*].(2014).Engineering a switch-on peptide to ricin A chain for increasing its specificity towards HIV-infected cells.BIOCHIMICA ET BIOPHYSICA ACTA,1840(3),958-963. |
| MLA | Au KY,et al."Engineering a switch-on peptide to ricin A chain for increasing its specificity towards HIV-infected cells".BIOCHIMICA ET BIOPHYSICA ACTA 1840.3(2014):958-963. |
入库方式： OAI收割
来源：昆明动物研究所
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