|author||Hugh I. Kim|
|journal||Journal of the American Chemical Society (J. Am. Chem. Soc., 2018, DOI: 10.1021/jacs.8b07864)|
Hyun Hee Lee (박사과정) Chae Eun Heo (박사과정)
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 cucurbituril (CB) 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 recognized the subtle structural differences between Neu5Gc and Neu5Ac. Distinct host-guest interactions between CB 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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