Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates
نویسندگان
چکیده
منابع مشابه
Evaluation of Factors Influencing Antibody Reduction for Development of Antibody Drug Conjugates
Background: Reduction/alkylation is one of the leading strategies for the development of antibody drug conjugates (ADCs). Precise control of the reduction process would not only yield a defined number of free thiols per antibody but also result in development of more homogenous conjugates. Methods: In the present study, we investigated the effect of various dithiothreitol (DTT) concentrations, ...
متن کاملMALDI-MS: a Rapid and Reliable Method for Drug-to-Antibody Ratio Determination of Antibody-Drug Conjugates
Background: It is believed that the loading value of anticancer drug conjugated to the monoclonal antibody, called drug-to-antibody ratio (DAR), is the main quality feature of antibody-drug conjugates. Methods: In this study, matrix assisted laser desorption/ionization mass spectrometry was used to determine the average molecular weight of trastuzumab and its three conjugated forms. The differe...
متن کاملIntracellular trafficking of new anticancer therapeutics: antibody–drug conjugates
Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great chal...
متن کاملSynthesis of Zinc Dimethyldithiocarbamate by Reductive Disulfide Bond Cleavage of Tetramethylthiuram Disulfide in Presence of Zn2+
The zinc(II) complex [Zn2(dmdtc)2(μ-dmdtc)2] has been synthesized directly from thiram ligand, containing a disulfide bond {dmdtc = N,N-dimethyldithiocarbamate; thiram = N,N-tetramethylthiuram disulfide}, and characterized by elemental analysis and spectroscopic methods. Surprisingly thiram, undergoes a reductive disulfide bond scission upon reaction with Zn2+ in methanolic media to give the [Z...
متن کاملRelationship between endosomes and lysosomes.
Delivery of endocytosed macromolecules to lysosomes occurs by means of direct fusion of late endosomes with lysosomes. This has been formally demonstrated in a cell-free content mixing assay using late endosomes and lysosomes from rat liver. There is evidence from electron microscopy studies that the same process occurs in intact cells. The fusion process results in the formation of hybrid orga...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2005
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.0509035102