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| PEGylated recombinant human interferon-omega as a long-acting antiviral agent: Structure, antiviral activity and pharmacokinetics | |
| Alternative Title | Antiviral Res. |
| Yu, Weili1,3; Yu, Changming2; Wu, Ling1,3; Fang, Ting2; Qiu, Rui1; Zhang, Jinlong2; Yu, Ting2; Fu, Ling2; Chen, Wei2; Hu, Tao1 | |
| 2014-08-01 | |
| Source Publication | ANTIVIRAL RESEARCH
 |
| ISSN | 0166-3542 |
| Volume | 108Issue:AUGPages:142-147 |
| Abstract | Recombinant human interferon-omega (rhIFN-omega) exhibits a potent antiviral activity. Because of poor pharmacokinetics (PK) of rhIEN-omega, frequent dosing of rhIFN-omega is necessitated to achieve the sustained antiviral efficacy. PEGylation can efficiently improve the PK of rhIFN-omega while substantially decrease its bioactivity. The structure, antiviral activity and PK of the PEGylated rhIEN-omega were measured to establish their relationship with PEGylation sites, polyethylene glycol (PEG) mass and PEG structure. Accordingly, N-terminus and the lysine residues were selected as the PEGylation sites. PEGs with M-w of 20 kDa and 40 kDa were used to investigate the effect of PEG mass. Linear and branched PEGs were used to investigate the effect of PEG structure. PEGylation decreased the antiviral activity of rhIEN-omega and improved its PK. The PEGylation sites determine the bioactivity of the PEGylated rhIFN-omega and the conjugated PEG mass determines the PK. N-terminally PEGylated rhIFN-omega with 40 kDa linear PEG maintains 21.7% of the rhIFN-omega antiviral activity with a half-life of 139.6 h. Thus, N-terminally PEGylated rhIFN-omega with linear 40 kDa PEG is a potential antiviral agent for long-acting treatment of the viral diseases. (C) 2014 Elsevier B.V. All rights reserved.; Recombinant human interferon-omega (rhIFN-omega) exhibits a potent antiviral activity. Because of poor pharmacokinetics (PK) of rhIEN-omega, frequent dosing of rhIFN-omega is necessitated to achieve the sustained antiviral efficacy. PEGylation can efficiently improve the PK of rhIFN-omega while substantially decrease its bioactivity. The structure, antiviral activity and PK of the PEGylated rhIEN-omega were measured to establish their relationship with PEGylation sites, polyethylene glycol (PEG) mass and PEG structure. Accordingly, N-terminus and the lysine residues were selected as the PEGylation sites. PEGs with M-w of 20 kDa and 40 kDa were used to investigate the effect of PEG mass. Linear and branched PEGs were used to investigate the effect of PEG structure. PEGylation decreased the antiviral activity of rhIEN-omega and improved its PK. The PEGylation sites determine the bioactivity of the PEGylated rhIFN-omega and the conjugated PEG mass determines the PK. N-terminally PEGylated rhIFN-omega with 40 kDa linear PEG maintains 21.7% of the rhIFN-omega antiviral activity with a half-life of 139.6 h. Thus, N-terminally PEGylated rhIFN-omega with linear 40 kDa PEG is a potential antiviral agent for long-acting treatment of the viral diseases. (C) 2014 Elsevier B.V. All rights reserved. |
| Keyword | Interferon-omega Antiviral Agent Pegylation Pharmacokinetics |
| Subtype | Article |
| WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
| DOI | 10.1016/j.antiviral.2014.06.003 |
| URL | 查看原文 |
| Indexed By | SCI |
| Language | 英语 |
| WOS Keyword | CHRONIC HEPATITIS-C ; VIRUS ; ALPHA ; STAPHYLOKINASE |
| WOS Research Area | Pharmacology & Pharmacy ; Virology |
| WOS Subject | Pharmacology & Pharmacy ; Virology |
| WOS ID | WOS:000340220400017 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Version | 出版稿 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/11594 |
| Collection | 研究所（批量导入） |
| Affiliation | 1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Beijing Inst Biotechnol, Beijing 100071, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100190, Peoples R China |
| Recommended Citation GB/T 7714 | Yu, Weili,Yu, Changming,Wu, Ling,et al. PEGylated recombinant human interferon-omega as a long-acting antiviral agent: Structure, antiviral activity and pharmacokinetics[J]. ANTIVIRAL RESEARCH,2014,108(AUG):142-147. |
| APA | Yu, Weili.,Yu, Changming.,Wu, Ling.,Fang, Ting.,Qiu, Rui.,...&Hu, Tao.(2014).PEGylated recombinant human interferon-omega as a long-acting antiviral agent: Structure, antiviral activity and pharmacokinetics.ANTIVIRAL RESEARCH,108(AUG),142-147. |
| MLA | Yu, Weili,et al."PEGylated recombinant human interferon-omega as a long-acting antiviral agent: Structure, antiviral activity and pharmacokinetics".ANTIVIRAL RESEARCH 108.AUG(2014):142-147. |
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| File Name/Size | DocType | Version | Access | License | ||
| PEGylated recombinan（781KB） | 限制开放 | CC BY-NC-SA | Application Full Text | |||
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