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

doi:10.1039/c6ob01751g

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	One-pot N-glycosylation remodeling of IgG with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates
	Tang, Feng 1,4; Yang, Yang 3,4; Tang, Yubo 2,4; Tang, Shuai 4; Yang, Liyun 1,4; Sun, Bingyang 3,4; Jiang, Bofeng 3,4; Dong, Jinhua 2; Liu, Hong4 ; Huang, Min4
刊名	ORGANIC & BIOMOLECULAR CHEMISTRY
	2016-10-28
卷号	14 期号:40 页码:9501-9518
ISSN号	1477-0520
DOI	10.1039/c6ob01751g
文献子类	Article
英文摘要	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.
资助项目	National Natural Science Foundation of China (NNSFC)[21372238] ; National Natural Science Foundation of China (NNSFC)[21572244] ; SIMM institute fund[CASIMM0120153004] ; "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020311]
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
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000385594100009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275845]
专题	生物技术药物研发中心（筹）药物安全性评价中心
通讯作者	Huang, Wei
作者单位	1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 2.Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China 3.ShanghaiTech Univ, iHuman Inst, 99 Haike Rd, Shanghai 201210, Peoples R China; 4.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;
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.