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

Hyun Hee L. Lee, Chae Eun Heo, Nari Seo, Seung Gyu Yun, Hyun Joo An, Hugh I. Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)16528-16534
Number of pages7
JournalJournal of the American Chemical Society
Volume140
Issue number48
DOIs
Publication statusPublished - 2018 Dec 5

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Glycoproteins
Sialic Acids
Mass spectrometry
Mass Spectrometry
Proteins
Acids
N-Acetylneuraminic Acid
Complexation
Assays
Therapeutics
Pharmaceutical Preparations
cucurbit(7)uril
N-glycolylneuraminic acid

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Accurate Quantification of N-Glycolylneuraminic Acid in Therapeutic Proteins Using Supramolecular Mass Spectrometry. / Lee, Hyun Hee L.; Heo, Chae Eun; Seo, Nari; Yun, Seung Gyu; An, Hyun Joo; Kim, Hugh I.

In: Journal of the American Chemical Society, Vol. 140, No. 48, 05.12.2018, p. 16528-16534.

Research output: Contribution to journalArticle

Lee, Hyun Hee L. ; Heo, Chae Eun ; Seo, Nari ; Yun, Seung Gyu ; An, Hyun Joo ; Kim, Hugh I. / Accurate Quantification of N-Glycolylneuraminic Acid in Therapeutic Proteins Using Supramolecular Mass Spectrometry. In: Journal of the American Chemical Society. 2018 ; Vol. 140, No. 48. pp. 16528-16534.
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