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An Integrated Strategy to Identify Tyrosine Sulfation from the Therapeutic Proteins. | LitMetric

An Integrated Strategy to Identify Tyrosine Sulfation from the Therapeutic Proteins.

J Am Soc Mass Spectrom

Discovery Analytical Research, Analytical Enabling Capabilities, Merck & Co., Inc., South San Francisco, California 94080, United States.

Published: December 2024

AI Article Synopsis

Article Abstract

Posttranslational modifications (PTMs) are potential critical quality attributes in biotherapeutic development, as they can affect drug efficacy and safety. Tyrosine sulfation plays a critical role in protein-protein interactions and has been found on many surface receptors as well as antibody complementarity-determining regions (CDR). However, the presence and function of tyrosine sulfation in therapeutic proteins have not been broadly investigated due to difficulties in detecting the modification. Here, we establish an integrated strategy to identify tyrosine sulfation in biotherapeutic proteins. In silico prediction was used to estimate possible modification sites, followed by the elucidation with intact LCMS and native SCX-MS. The combination of these three steps takes less than 1 h, which provides quick and confident preliminary detection of potential CQAs. Taking NB1 as an example, three +80 Da mass shifts were observed from intact mass analysis and three acidic peaks were monitored by SCX, allowing confirmation of modification as either phosphorylation or sulfation. Peptide mapping, Fe-IMAC enrichment, and dephosphorylation were further conducted to provide improved signal intensity and differentiation of modification such as sulfation or phosphorylation. With this integrated strategy, we were able to identify for the first time both tyrosine sulfation and serine phosphorylation in one therapeutic protein.

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Source
http://dx.doi.org/10.1021/jasms.4c00303DOI Listing

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