Divinylsulfonamides enable the construction of homogeneous antibody-drug conjugates
Huang, Rong1,2; Sheng, Yao1; Wei, Ding1,2,3; Lu, Wenwen1,2; Xu, Zili1,2; Chen, Hongli1; Jiang, Biao1
2020-10-06
Source PublicationBIOORGANIC & MEDICINAL CHEMISTRY
ISSN0968-0896
EISSN1464-3391
Volume28Issue:23Pages:115793
Status已发表
DOI10.1016/j.bmc.2020.115793
Abstract

Methods that site-specifically attach payloads to an antibody with controlled DAR (Drug-Antibody Ratio) are highly desirable for the generation of homogeneous antibody-drug conjugates (ADCs). We describe the use of N-phenyl-divinylsulfonamide scaffold as a linker platform to site-specifically construct homogeneous DAR four ADCs through a disulfide re-bridging approach. Several monomethyl auristatin E (MMAE)-linkers were synthesized and the drug-linkers that contain electron-donating groups on the phenyl of the linker showed high stability. Her2-targeted MMAE-linker-herceptin and EGFR targeted MMAE-linker-cetuximab conjugates were prepared. The conjugates demonstrated high efficacy and selectivity for killing target-positive cancer cells in vitro. The EGFR-targeted conjugates also showed significant antitumor activities in vivo.

KeywordDivinylsulfonamides Antibody-drug conjugates Selectivity
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
WOS IDWOS:000604559300019
PublisherPERGAMON-ELSEVIER SCIENCE LTD
WOS KeywordDISULFIDE BONDS ; NEXT-GENERATION ; PEPTIDES
Original Document TypeArticle
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125964
Collection生命科学与技术学院_硕士生
免疫化学研究所_特聘教授组_抗体化学实验室
免疫化学研究所_特聘教授组_蒋华良组
物质科学与技术学院_博士生
Co-First AuthorSheng, Yao
Corresponding AuthorChen, Hongli; Jiang, Biao
Affiliation1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China;
2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China;
3.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai 201210, Peoples R China
First Author AffilicationShanghai Institute for Advanced Immunochemical Studies
Corresponding Author AffilicationShanghai Institute for Advanced Immunochemical Studies
First Signature AffilicationShanghai Institute for Advanced Immunochemical Studies
Recommended Citation
GB/T 7714
Huang, Rong,Sheng, Yao,Wei, Ding,et al. Divinylsulfonamides enable the construction of homogeneous antibody-drug conjugates[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2020,28(23):115793.
APA Huang, Rong.,Sheng, Yao.,Wei, Ding.,Lu, Wenwen.,Xu, Zili.,...&Jiang, Biao.(2020).Divinylsulfonamides enable the construction of homogeneous antibody-drug conjugates.BIOORGANIC & MEDICINAL CHEMISTRY,28(23),115793.
MLA Huang, Rong,et al."Divinylsulfonamides enable the construction of homogeneous antibody-drug conjugates".BIOORGANIC & MEDICINAL CHEMISTRY 28.23(2020):115793.
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