亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Chemoenzymatic Glycoengineering of Intact IgG Antibodies for Gain of Functions

化学 抗体 生物化学 免疫球蛋白G 生物 免疫学
作者
Wei Huang,John P. Giddens,Shuquan Fan,Christian Toonstra,Lai‐Xi Wang
出处
期刊:Journal of the American Chemical Society [American Chemical Society]
卷期号:134 (29): 12308-12318 被引量:298
标识
DOI:10.1021/ja3051266
摘要

The fine structures of Fc N-glycans can modulate the effector functions of IgG antibodies. It has been demonstrated that lack of the core fucose on the Fc N-glycans leads to drastic enhancement of antibody-dependent cellular cytotoxicity (ADCC), while terminal α2,6-sialylation of Fc glycan plays a critical role for the anti-inflammatory activity of human intravenous immunoglobulin (IVIG). We describe in this paper a highly efficient chemoenzymatic method for site-selective Fc glycoengineering of intact monoclonal antibody and IVIG. Two new glycosynthase mutants (EndoS-D233A and D233Q) were generated by site-directed mutagenesis of EndoS (an endoglycosidase from Streptococcus pyogenes) and were found to be capable of efficiently transferring predefined N-glycans from corresponding glycan oxazolines to the Fc-deglycosylated intact IgGs without product hydrolysis. As a model study, rituximab (a therapeutic monoclonal antibody) was successfully transformed from mixtures of G0F, G1F, and G2F glycoforms to well-defined homogeneous glycoforms, including a fully sialylated (S2G2F) glycoform that may gain anti-inflammatory activity, a nonfucosylated G2 glycoform that showed significantly enhanced FcγIIIa receptor-binding activity, and an azido-tagged glycoform that can be further transformed into other glycoforms. We also found that EndoS could selectively remove the Fc N-glycans in the presence of FAB glycosylation. This finding, coupled with the remarkable transglycosylation activity of the EndoS glycosynthase mutants, permitted a highly selective glycoengineering of the IVIG's Fc glycans into a fully sialylated Fc glycoform, which may possess significantly enhanced anti-inflammatory activity. The glycoengineering approach described here provides a general platform to modulate the effector functions of IgG antibodies, enabling the optimization of therapeutic efficacy and gain of new functions of monoclonal antibodies and IVIG.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
科研通AI5应助Ma采纳,获得10
16秒前
忧伤的绍辉完成签到 ,获得积分10
17秒前
隐形曼青应助易四夕采纳,获得10
21秒前
1分钟前
易四夕发布了新的文献求助10
1分钟前
1分钟前
1分钟前
Ma发布了新的文献求助10
1分钟前
1分钟前
随机子发布了新的文献求助10
1分钟前
1分钟前
Ava应助科研通管家采纳,获得10
1分钟前
科目三应助科研通管家采纳,获得10
1分钟前
科研通AI2S应助科研通管家采纳,获得10
1分钟前
Ma发布了新的文献求助10
2分钟前
Ma完成签到,获得积分10
2分钟前
3分钟前
易四夕发布了新的文献求助10
3分钟前
3分钟前
3分钟前
英姑应助王大壮采纳,获得10
3分钟前
SciGPT应助科研通管家采纳,获得10
3分钟前
3分钟前
4分钟前
4分钟前
Mine发布了新的文献求助10
4分钟前
王大壮发布了新的文献求助10
4分钟前
Mine完成签到,获得积分10
4分钟前
郗妫完成签到,获得积分10
4分钟前
王大壮发布了新的文献求助10
4分钟前
科研通AI5应助Mine采纳,获得30
4分钟前
4分钟前
852应助美好颜采纳,获得10
5分钟前
纯情女大完成签到 ,获得积分10
5分钟前
5分钟前
5分钟前
FashionBoy应助科研通管家采纳,获得30
5分钟前
丘比特应助科研通管家采纳,获得10
5分钟前
斯文败类应助科研通管家采纳,获得10
5分钟前
赘婿应助科研通管家采纳,获得10
5分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968492
求助须知:如何正确求助?哪些是违规求助? 3513278
关于积分的说明 11167214
捐赠科研通 3248660
什么是DOI,文献DOI怎么找? 1794386
邀请新用户注册赠送积分活动 875030
科研通“疑难数据库(出版商)”最低求助积分说明 804638