A Simple and Efficient Method to Generate Dual Site-Specific Conjugation ADCs with Cysteine Residue and an Unnatural Amino Acid.
Bioconjug Chem
; 32(6): 1094-1104, 2021 06 16.
Article
en En
| MEDLINE
| ID: mdl-34013721
ABSTRACT
Antibody-drug conjugates (ADCs) are complex pharmaceutical molecules that combine monoclonal antibodies with biologically active drugs through chemical linkers. ADCs are designed to specifically kill disease cells by utilizing the target specificity of antibodies and the cytotoxicity of chemical drugs. However, the traditional ADCs were only applied to a few disease targets because of some limitations such as the huge molecular weight, the uncontrollable coupling reactions, and a single mechanism of action. Here we report a simple, one-pot, successive reaction method to produce dual payload conjugates with the site-specifically engineered cysteine and p-acetyl-phenylalanine using Herceptin (trastuzumab), an anti-HER2 antibody drug widely used for breast cancer treatment, as a tool molecule. This strategy enables antibodies to conjugate with two mechanistically distinct cytotoxic drugs through different functional groups sequentially, therefore, rendering the newly designed ADCs with functional diversity and the potential to overcome drug resistance and enhance the therapeutic efficacy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoconjugados
/
Cisteína
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China