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	PEGylated recombinant human interferon-omega as a long-acting antiviral agent: Structure, antiviral activity and pharmacokinetics
	Yu, Weili1,3; Yu, Changming2; Wu, Ling1,3; Fang, Ting2; Qiu, Rui1; Zhang, Jinlong2; Yu, Ting2; Fu, Ling2; Chen, Wei2; Hu, Tao1
刊名	ANTIVIRAL RESEARCH
	2014-08-01
卷号	108期号:AUG页码:142-147
关键词	Interferon-omega Antiviral agent PEGylation Pharmacokinetics
ISSN号	0166-3542
其他题名	Antiviral Res.
中文摘要	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.
英文摘要	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.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Pharmacology & Pharmacy ; Virology
研究领域[WOS]	Pharmacology & Pharmacy ; Virology
关键词[WOS]	CHRONIC HEPATITIS-C ; VIRUS ; ALPHA ; STAPHYLOKINASE
收录类别	SCI
原文出处	://WOS:000340220400017
语种	英语
WOS记录号	WOS:000340220400017
公开日期	2014-09-30
内容类型	期刊论文
版本	出版稿
源URL	[http://ir.ipe.ac.cn/handle/122111/11594]
专题	过程工程研究所_研究所（批量导入）
作者单位	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
推荐引用方式 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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