IMECH-IR  > 国家微重力实验室
Molecular Modeling and Affinity Determination of scFv Antibody: Proper Linker Peptide Enhances Its Activity
Gu X; Jia XL(贾潇凌); Feng JN; Shen BF; Huang Y; Geng SS; Sun YX; Wang Y; Li Y; Long M(龙勉); Long M(龙勉)
2010
发表期刊Annals of Biomedical Engineering
卷号38期号:2页码:537-549
ISSN0090-6964
摘要One of existing strategies to engineer active antibody is to link VH and VL domains via a linker peptide. How the composition, length, and conformation of the linker affect antibody activity, however, remains poorly understood. In this study, a dual approach that coordinates molecule modeling, biological measurements, and affinity evaluation was developed to quantify the binding activity of a novel stable miniaturized anti-CD20 antibody or singlechain fragment variable (scFv) with a linker peptide. Upon computer-guided homology modeling, distance geometry analysis, and molecular superimposition and optimization, three new linker peptides PT1, PT2, and PT3 with respective 7, 10, and 15 residues were proposed and three engineered antibodies were then constructed by linking the cloned VH and VL domains and fusing to a derivative of human IgG1. The binding stability and activity of scFv-Fc chimera to CD20 antigen was quantified using a micropipette adhesion frequency assay and a Scatchard analysis. Our data indicated that the binding affinity was similar for the chimera with PT2 or PT3 and ~24-fold higher than that for the chimera with PT1, supporting theoretical predictions in molecular modeling. These results further the understanding in the impact of linker peptide on antibody structure and activity.
关键词Linker Peptide Molecular Modeling Micropipette Adhesion Frequency Scatchard Analysis Binding Affinity
学科领域生物力学
DOI10.1007/s10439-009-9810-2
收录类别SCI
语种英语
WOS记录号WOS:000274237000024
关键词[WOS]LIGAND BINDING-KINETICS ; SINGLE-CHAIN ANTIBODY ; ALKALINE-PHOSPHATASE ; CRYSTAL-STRUCTURE ; ESCHERICHIA-COLI ; FLOW-CYTOMETRY ; FV FRAGMENT ; CELL-CYCLE ; ANTIGEN ; DESIGN
WOS研究方向Engineering
WOS类目Engineering, Biomedical
引用统计
被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://dspace.imech.ac.cn/handle/311007/33025
专题国家微重力实验室
通讯作者Long M(龙勉)
推荐引用方式
GB/T 7714
Gu X,Jia XL,Feng JN,et al. Molecular Modeling and Affinity Determination of scFv Antibody: Proper Linker Peptide Enhances Its Activity[J]. Annals of Biomedical Engineering,2010,38(2):537-549.
APA Gu X.,Jia XL.,Feng JN.,Shen BF.,Huang Y.,...&龙勉.(2010).Molecular Modeling and Affinity Determination of scFv Antibody: Proper Linker Peptide Enhances Its Activity.Annals of Biomedical Engineering,38(2),537-549.
MLA Gu X,et al."Molecular Modeling and Affinity Determination of scFv Antibody: Proper Linker Peptide Enhances Its Activity".Annals of Biomedical Engineering 38.2(2010):537-549.
条目包含的文件 下载所有文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
Molecular modeling a(616KB)期刊论文作者接受稿开放获取CC BY-NC-SA浏览 下载
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Gu X]的文章
[Jia XL(贾潇凌)]的文章
[Feng JN]的文章
百度学术
百度学术中相似的文章
[Gu X]的文章
[Jia XL(贾潇凌)]的文章
[Feng JN]的文章
必应学术
必应学术中相似的文章
[Gu X]的文章
[Jia XL(贾潇凌)]的文章
[Feng JN]的文章
相关权益政策
暂无数据
收藏/分享
文件名: Molecular modeling and affinity determination.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。