Impact of Maleimide Disubstitution on Chemical and Biological Characteristics of HER2 Antibody-Drug Conjugates.

ABSTRACT: Antibody-drug conjugates (ADCs) are the spearhead of targeted therapies. According to the technology used, the conjugation of a cytotoxic drug to an antibody can produce suboptimal heterogeneous species, impacting the overall efficacy. Herein, we describe the synthesis of HER2-targeting ADCs with three disulfide rebridging heads, allowing homogeneous and site-specific bioconjugation: dibromomaleimide (DBM), dithiomaleimide (DTM), and hybrid thio-bromomaleimide (TBM) chemical bricks to combine the properties of both previously used heads. The primary purpose of this study was to compare the reactivity of these three chemical bricks in the bioconjugation process. Then, the resulting ADCs were evaluated in terms of physicochemical stability, binding, and biological activity. We have demonstra

SUBMITTER: Feuillatre O 

PROVIDER: S-EPMC6990629 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature