Characterization of Positional Isomers of Interchain Cysteine Linked Antibody-Drug Conjugates by High-Resolution Mass Spectrometry

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.

Department(s)

Chemistry

Research Center/Lab(s)

Center for Research in Energy and Environment (CREE)

International Standard Serial Number (ISSN)

1520-6882

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2019 NLM (Medline), All rights reserved.

Publication Date

01 Jul 2019

PubMed ID

31247726

Link to Full Text

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