One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates

doi:10.1039/c6ob01751g

KMS > iHuman研究所

	One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates
	Tang, Feng 1,2; Yang, Yang1,3 ; Tang, Yubo 1,4; Tang, Shuai 1; Yang, Liyun 1,2; Sun, Bingyang 1,3; Jiang, Bofeng 1,3; Dong, Jinhua 4; Liu, Hong 1; Huang, Min 1; Geng, Mei-Yu 1; Huang, Wei1,3
	2016-10-28
发表期刊	ORGANIC & BIOMOLECULAR CHEMISTRY (IF:2.9[JCR-2023],2.8[5-Year])
ISSN	1477-0520
卷号	14 期号:40 页码:9501-9518
发表状态	已发表
DOI	10.1039/c6ob01751g
摘要	Chemoenzymatic transglycosylation catalyzed by endo-S mutants is a powerful tool for in vitro glycoengineering of therapeutic antibodies. In this paper, we report a one-pot chemoenzymatic synthesis of glycoengineered Herceptin using an egg-yolk sialylglycopeptide (SGP) substrate. Combining this one-pot strategy with novel non-natural SGP derivatives carrying azido or alkyne tags, glycosite-specific conjugation was enabled for the development of new antibody-drug conjugates (ADCs). The site-specific ADCs and semi-site-specific dual-drug ADCs were successfully achieved and characterized with SDS-PAGE, intact antibody or ADC mass spectrometry analysis, and PNGase-F digestion analysis. Cancer cell cytotoxicity assay revealed that small-molecule drug release of these ADCs relied on the cleavable Val-Cit linker fragment embedded in the structure. These results represent a new approach for glycosite-specific and dual-drug ADC design and rapid synthesis, and also provide the structural requirement for their biologic activities.
收录类别	SCI ; IC ; EI
WOS研究方向	Chemistry
WOS类目	Chemistry, Organic
WOS记录号	WOS:000385594100009
出版者	ROYAL SOC CHEMISTRY
EI入藏号	20164302929965
EI主题词	Drug products ; Glycosylation ; Mass spectrometry
EI分类号	Biology:461.9 ; Immunology:461.9.1 ; Chemistry:801 ; Biochemistry:801.2
WOS关键词	ENDOHEXOSAMINIDASE-CATALYZED GLYCOSYLATION ; DEPENDENT CELLULAR CYTOTOXICITY ; SITE-SPECIFIC CONJUGATION ; IN-VITRO GALACTOSYLATION ; FREE CLICK CHEMISTRY ; FC-GAMMA-RIII ; ANTIINFLAMMATORY ACTIVITY ; CHEMOENZYMATIC SYNTHESIS ; THERAPEUTIC ANTIBODIES ; EFFECTOR FUNCTIONS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1663
专题	iHuman研究所生命科学与技术学院_PI研究组_杨扬组 iHuman研究所_PI研究组_程建军组
通讯作者	Huang, Wei
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, iHuman Inst, 99 Haike Rd, Shanghai 201210, Peoples R China 4.Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China
通讯作者单位	iHuman研究所
推荐引用方式 GB/T 7714	Tang, Feng,Yang, Yang,Tang, Yubo,et al. One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2016,14(40):9501-9518.
APA	Tang, Feng.,Yang, Yang.,Tang, Yubo.,Tang, Shuai.,Yang, Liyun.,...&Huang, Wei.(2016).One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates.ORGANIC & BIOMOLECULAR CHEMISTRY,14(40),9501-9518.
MLA	Tang, Feng,et al."One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates".ORGANIC & BIOMOLECULAR CHEMISTRY 14.40(2016):9501-9518.