Journal
BIOANALYSIS
Volume 10, Issue 20, Pages 1651-1666Publisher
FUTURE SCI LTD
DOI: 10.4155/bio-2018-0201
Keywords
alternative scaffold; ADC; antibody-drug conjugate; bioanalysis; CDC; Centyrin; Centyrin-drug conjugate; conjugation; LC-MS; protein-drug conjugate; PDC; quantitation
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Aim: Alternative scaffold proteins have emerged as novel platforms for development of therapeutic applications. One such application is in protein-drug conjugates (PDCs), which are analogous to antibody-drug conjugates. Methodology: Liquid chromatography-mass spectrometry methods for quantitation of total protein, conjugate and free payload for a PDC based on Centyrin scaffold were developed. Tryptic peptides generated from a region of the Centyrin that does not contain a conjugation site, and another that has the conjugation site with the linker-payload attached were used as surrogates of the total and conjugated Centyrin, respectively. Conclusion: The methods were successfully applied to analysis of samples from mice to quantify the plasma and tissue concentrations. This same workflow can potentially be applied to other PDCs and site-specific antibody-drug conjugates.
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