Accurate Quantification of N‑Glycolylneuraminic Acid in Therapeutic Proteins Using Supramolecular Mass Spectrometry

Practical applications of innovative host–guest systems are challenging because of unexpected guest competitors and/or subtle environmental differences. Herein, a supramolecular mass spectrometry (MS)-based method using a synthetic host, cucurbit[7]­uril (CB[7]), was developed for identifying and qu...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2018-12, Vol.140 (48), p.16528-16534
Main Authors: Lee, Hyun Hee L, Heo, Chae Eun, Seo, Nari, Yun, Seung Gyu, An, Hyun Joo, Kim, Hugh I
Format: Article
Language:English
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Summary:Practical applications of innovative host–guest systems are challenging because of unexpected guest competitors and/or subtle environmental differences. Herein, a supramolecular mass spectrometry (MS)-based method using a synthetic host, cucurbit[7]­uril (CB[7]), was developed for identifying and quantifying N-glycolylneuraminic acid (Neu5Gc) in therapeutic glycoproteins, which critically reduces drug efficacy. The development of a reliable derivatization-free analytical method for Neu5Gc is highly challenging because of the interference by the abundant N-acetylneuraminic acid (Neu5Ac). CB[7] recognized the subtle structural differences between Neu5Gc and Neu5Ac. Distinct host–guest interactions between CB[7] and the two sialic acids produced a highly linear relationship between the complexation and concentration proportions of the two sialic acids in MS. Furthermore, the developed method had sub-picomolar quantification limits and a wide range of applicability for diverse glycoproteins, demonstrating the potential utility of this method as a reliable assay of Neu5Gc in therapeutic glycoproteins.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.8b07864