Enfuvirtide-peg conjugate: a potent hiv fusion inhibitor with improved pharmacokinetic properties
文献类型：期刊论文
| 作者 | Cheng, Shuihong1,2; Wang, Yan3; Zhang, Zhenxing1,4; Lv, Xun1; Gao, George F.1,5; Shao, Yiming3; Ma, Liying3; Li, Xuebing1,2,5 |
| 刊名 | European journal of medicinal chemistry
 |
| 出版日期 | 2016-10-04 |
| 卷号 | 121页码:232-237 |
| 关键词 | Conjugation Enfuvirtide Fusion inhibitor Human immunodeficiency virus Pharmacokinetics Poly(ethylene glycol) |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.05.027 |
| 通讯作者 | Ma, liying(mal@chinaaids.cn) ; Li, xuebing(lixb@im.ac.cn) |
| 英文摘要 | Enfuvirtide (enf) is a clinically used peptide drug for the treatment of hiv infections, but its poor pharmacokinetic profile (t-1/2 =1.5 h in rats) and low aqueous solubility make the therapy expensive and inconvenience. in this study, we present a simple and practical strategy to address these problems by conjugating enf with polyethylene glycol (peg). site-specific attachment of a 2 kda peg at the n-terminus of enf resulted in an enf-peg (ep) conjugate with high solubility (>= 3 mg/ml) and long half-life in rats (t-1/2 = 16.1 h). this conjugate showed similar antiviral activity to enf against various primary hiv 1 isolates (ec50 = 6-91 nm). mechanistic studies suggested the sources of the antiviral potency. the conjugate bound to a functional domain of the hiv gp41 protein in a helical conformation with high affinity (k-d = 307 nm), thereby inhibiting the gp41-mediated fusion of viral and host-cell membranes. as peg conjugation has advanced many bioactive proteins and peptides into clinical applications, the ep conjugate described here represents a potential new treatment for hiv infections that may address the unmet medical needs associated with the current enf therapy. (c) 2016 elsevier masson sas. all rights reserved. |
| WOS关键词 | MEMBRANE-FUSION ; COILED-COIL ; HALF-LIFE ; MULTIFUNCTIONAL DOMAINS ; DRUG-DELIVERY ; SPIKE PROTEIN ; PEPTIDE ; VIRUS ; PEGYLATION ; DESIGN |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Medicinal |
| 语种 | 英语 |
| WOS记录号 | WOS:000382269700020 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375365 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Ma, Liying; Li, Xuebing |
| 作者单位 | 1.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China 2.Jiangxi Normal Univ, Natl Engn Res Ctr Carbohydrate Synth, Nanchang 330022, Peoples R China 3.Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Natl Ctr AIDS STD Control & Prevent, Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing 102206, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci CASCIRE, Ctr Influenza Res & Early Warning, Beijing 100101, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Shuihong,Wang, Yan,Zhang, Zhenxing,et al. Enfuvirtide-peg conjugate: a potent hiv fusion inhibitor with improved pharmacokinetic properties[J]. European journal of medicinal chemistry,2016,121:232-237. |
| APA | Cheng, Shuihong.,Wang, Yan.,Zhang, Zhenxing.,Lv, Xun.,Gao, George F..,...&Li, Xuebing.(2016).Enfuvirtide-peg conjugate: a potent hiv fusion inhibitor with improved pharmacokinetic properties.European journal of medicinal chemistry,121,232-237. |
| MLA | Cheng, Shuihong,et al."Enfuvirtide-peg conjugate: a potent hiv fusion inhibitor with improved pharmacokinetic properties".European journal of medicinal chemistry 121(2016):232-237. |
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来源：中国科学院大学
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