One-pot n-glycosylation remodeling of igg with non-natural sialylglycopeptides enables glycosite-specific and dual-payload antibody-drug conjugates
文献类型:期刊论文
作者 | Tang, Feng1,2; Yang, Yang1,3; Tang, Yubo1,4; Tang, Shuai1; Yang, Liyun1,2; Sun, Bingyang1,3; Jiang, Bofeng1,3; Dong, Jinhua4; Liu, Hong1; Huang, Min1 |
刊名 | Organic & biomolecular chemistry |
出版日期 | 2016-10-28 |
卷号 | 14期号:40页码:9501-9518 |
ISSN号 | 1477-0520 |
DOI | 10.1039/c6ob01751g |
通讯作者 | Huang, wei(huangwei@simm.ac.cn) |
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. |
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 |
WOS类目 | Chemistry, Organic |
语种 | 英语 |
出版者 | ROYAL SOC CHEMISTRY |
WOS记录号 | WOS:000385594100009 |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2374782 |
专题 | 中国科学院大学 |
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 |
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. |
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来源:中国科学院大学
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