Professor Zhenqing Zhang's Group published Cover Paper in Anal. Chem.
Recently, Professor Zhang Zhenqing's research group from Soochow University published a cover paper in Analytical Chemistry: Glycan Mapping of Low-Molecular-Weight Heparin Using Mass Spectral Correction Based on Chromatography Fitting with Glycomapping Software. The self-developed Glycomapping software is the highlight of this paper, which can be used for the analysis of low molecular weight heparin and even more other complex polysaccharides. On the one hand, ultra-high performance size exclusion chromatography is applied, the separation chromatogram of multiple peaks is reconstructed by repeated iterative fitting, and a complex chromatogram can be fitted with Glycomapping, significantly improving resolution and confirming an accurate distribution range for each size of glycan within enoxaparin. On the other hand, a virtual mass spectrum database of glycans in enoxaparin is established for the initial search, and randomly matched MS data can be corrected with the constraint of the corresponding chromatographic retention time range to remove the false positive data. This work enabled accurate and automatic analysis of heterogeneous mixtures of natural glycans, such as LMWHs and other complex oligosaccharides and polysaccharides.
Heparin and low molecular weight heparin are important anticoagulant drugs widely used in the clinic with a long history. They are essentially glycosaminoglycans whose anticoagulant activities are related to molecular weight, constituents, and sulfates. However, structural analysis for heparins has always been difficult in this field, and the previously reported structure analytical methods have limitations, which greatly obstruct the in-depth understanding and further application of heparins.
The Glycomapping mentioned in this paper is a self-developed software by Professor Zhang Zhenqing's group with independent intellectual property rights. In this work, ultra-high performance size exclusion chromatography (UPSEC), which has stable and predictable chromatographic behavior, is used to separate low molecular weight heparin drugs. Relied on the Glycomapping software, the separating chromatogram of multiple peaks is reconstructed through the repeated iterative fitting so that the unseparated peaks, shoulder peaks, and hidden peaks all achieve the baseline separation.Simultaneously, the Glycomapping software search and match detected mass spectrum data with the polysaccharide theoretical database built based on the De novo strategy, eliminating false positives mass spectrum data according to the accurate chromatographic retention times of oligosaccharide with different degrees ofpolymerization. Finally, the true oligosaccharide composition is obtained based on the assigned and corrected mass spectrum data.
The Glycomapping software is based on ultra-high performance liquid chromatography-mass spectrometry, realizing the baseline separation and qualitative and quantitative analysis of oligosaccharides in low molecular weight heparin automatically. The software has been successfully applied in analyzing enoxaparin sodium, nadroparin calcium, dalteparin sodium, and other low molecular weight heparins. It also achieves great success in the structural consistency evaluation of enoxaparin products with different production processes and different sources, providing depth and detailed structure information. This work lays a solid foundation for the automated analysis of heterogeneous mixtures such as heparin, chondroitin sulfate, sulfated fucoidan, etc. What's more, the software provides a feasible strategy for automatic structural analysis of complex polysaccharides, which has important significance and great commercial value, as the automatic structural analysis strategy provides convenience for the consistent evaluation of products in the pharmaceutical, food, and other industries. It is something to look forward to the application of this new automatic structural analysis technology based on Glycomapping software, which will improve the efficiency and accuracy of the consistency evaluation for products and also provide analytical technology in structure for developing more new products.
This work is published in Analytical Chemistry. Yan Na, a Master student at Soochow University, is the first author of the paper, and Professor Zhang Zhenqing and Assistant Researcher Yi Lin are the co-corresponding authors.
Co-corresponding authors：
Zhenqing Zhang is a doctoral tutor and distinguished professor at Soochow University. He has won honors as a Distinguished Professor of Jiangsu Province, Innovative and Entrepreneurial talents of Jiangsu Province, Six Peak Talents of Jiangsu Province, etc. He is currently a CDE evaluation expert for glycan new drugs and serves as an expert member of the Pharmaceutical Subcommittee of the Chinese Pharmaceutical Association. He has been engaged in the research of glycan drugs for more than 20 years and has achieved fruitful results in the fields of analytical methodology, quality control, structural analysis, and bio-activity research. He has published nearly 100 SCI papers, including top journals in the fields, such as Nature Biotech, JACS, PNAS, Anal. Chem, etc.; and he has applied for over 50 patents and authorized nearly 20 patents, and assisted more than ten companies in completing the structural consistency research of various generic heparin drugs. Moreover, he has led the research on the structure analysis, product process, quality control, and pharmacokinetics in vivo of GV-971 to facilitate the first appearance of GV-971 on the market.
Linkage：http://pharm.suda.edu.cn/93/a3/c28908a496547/page.htm
Lin Yi is an assistant researcher at Soochow University. In 2014, she graduated from Soochow University with a bachelor's degree. In 2020, she graduated from Soochow University with a Ph.D. degree. She trained in the Eshelman School of Pharmacy of the University of North Carolina at Chapel Hill as a visiting scholar during 2018-2020. Since September 2020, she has worked in the School of Pharmacy of Soochow University. She presides over projects such as the National Natural Science Foundation of China, Innovative and Entrepreneurial Doctor of Jiangsu Province, Sequence analysis of enoxaparin Sodium, and Research on the interaction with PF4, etc. She has published more than 20 SCI papers as the first author and corresponding author in Analytical Chemistry, Carbohydrate Polymers, Journal of Chromatography A, Journal of the American Society for Mass Spectrometry, etc. She has applied for 10 patents and authorized 7 patents. Her research interest includes structure and activity research of glycosaminoglycan, sequence structure analysis, and structure-activity relationship in immunomodulation of natural polysaccharides.
The first author：
Na Yan is a graduate student of the School of Pharmaceutical Science, Soochow University. she graduated with a bachelor's degree In 2019 and a master's degree in 2022 at Soochow University. She has won honors such as the National Graduate Scholarship, the Outstanding Graduate Student, the Xiexin Award Scholarship, the Hehe Award Scholarship,the Grand Prize of Academic Scholarship, the Outstanding graduate of Soochow University, etc. She has published 6 SCI papers, of which 2 SCI papers were published in Analytical Chemistry and Food Chemistry as the first author. She also applied for 6 patents, and 5 were authorized.
Publication information：
Anal. Chem. 2022,94, 38, 13000
Publication Date: September 14, 2022
https://doi.org/10.1021/acs.analchem.2c01579
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