Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: Tetra-conjugation or PEG as the linker

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	Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: Tetra-conjugation or PEG as the linker
	Li, Chunju 1,2; Lin, Qixun 2; Wang, Jun 1; Shen, Lijuan 1; Ma, Guanghui 1; Su, Zhiguo 1; Hu, Tao 1
刊名	JOURNAL OF BIOTECHNOLOGY
	2012-12-31
卷号	162 期号:2-3 页码:283-288
关键词	Ribonuclease A Albumin conjugation PEG linker Tetravalent
ISSN号	0168-1656
通讯作者	Hu, T
英文摘要	Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K-m and the highest relative enzymatic activity and k(cat)/K-m in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. (C) 2012 Elsevier B. V. All rights reserved.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biotechnology & Applied Microbiology
研究领域[WOS]	Biotechnology & Applied Microbiology
关键词[WOS]	HUMAN SERUM-ALBUMIN ; CHRONIC HEPATITIS-C ; FUSION PROTEIN ; PEGYLATION ; HEMOGLOBIN ; DESIGN ; RNA ; ALBINTERFERON-ALPHA-2B ; INTERFERON ; POTENT
收录类别	SCI
语种	英语
WOS记录号	WOS:000311642000014
公开日期	2013-10-10
内容类型	期刊论文
版本	出版稿
源URL	[http://ir.ipe.ac.cn/handle/122111/3140]
专题	过程工程研究所_生化工程国家重点实验室
作者单位	1.Chinese Acad Sci, Natl Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China 2.Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China
推荐引用方式 GB/T 7714	Li, Chunju,Lin, Qixun,Wang, Jun,et al. Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: Tetra-conjugation or PEG as the linker[J]. JOURNAL OF BIOTECHNOLOGY,2012,162(2-3):283-288.
APA	Li, Chunju.,Lin, Qixun.,Wang, Jun.,Shen, Lijuan.,Ma, Guanghui.,...&Hu, Tao.(2012).Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: Tetra-conjugation or PEG as the linker.JOURNAL OF BIOTECHNOLOGY,162(2-3),283-288.
MLA	Li, Chunju,et al."Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: Tetra-conjugation or PEG as the linker".JOURNAL OF BIOTECHNOLOGY 162.2-3(2012):283-288.