Characterization of Positional Isomers of Interchain Cysteine Linked Antibody-Drug Conjugates by High-Resolution Mass Spectrometry.
Anal Chem
; 91(13): 8558-8563, 2019 07 02.
Article
en En
| MEDLINE
| ID: mdl-31247726
ABSTRACT
Interchain cysteine linked antibody-drug conjugates (ADCs) are emerging therapeutic products that antagonize cancers. The toxic payloads are selectively linked to the interchain cysteines and generate heterogeneous mixtures of positional isomers. These positional isomers might contribute differently to the therapeutic efficacy because of the variation in conjugation stability, and thus they need to be well characterized. However, the characterization of the positional isomers of interchain cysteine linked ADCs is very challenging, mainly because of the high similarity between those isomers. In this research, we developed a novel mass spectrometry method for the characterization of positional isomers of interchain cysteine linked ADCs. The subunit analysis and the bottom-up analysis provided abundant information about the drug numbers and drug linking positions on each chain. Because the method can provide accurate data on drug linking numbers and positions on each chain, it will be very useful for researchers in cancer drug development and cancer treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Espectrometría de Masas
/
Preparaciones Farmacéuticas
/
Cromatografía Líquida de Alta Presión
/
Inmunoconjugados
/
Cisteína
/
Anticuerpos Monoclonales
Límite:
Humans
Idioma:
En
Revista:
Anal Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos