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 language | English |
|---|---|
| Pages (from-to) | 16528-16534 |
| Number of pages | 7 |
| Journal | Journal of the American Chemical Society |
| Volume | 140 |
| Issue number | 48 |
| DOIs | |
| Publication status | Published - 2018 Dec 5 |
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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 journal › Article
}
TY - JOUR
T1 - Accurate Quantification of N-Glycolylneuraminic Acid in Therapeutic Proteins Using Supramolecular Mass Spectrometry
AU - Lee, Hyun Hee L.
AU - Heo, Chae Eun
AU - Seo, Nari
AU - Yun, Seung Gyu
AU - An, Hyun Joo
AU - Kim, Hugh I.
PY - 2018/12/5
Y1 - 2018/12/5
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.8b07864
DO - 10.1021/jacs.8b07864
M3 - Article
C2 - 30153004
AN - SCOPUS:85053674262
VL - 140
SP - 16528
EP - 16534
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 48
ER -