Expedient Synthesis of a Library of Heparan Sulfate-Like “Head-to-Tail” Linked Multimers for Structure and Activity Relationship Studies
Authors:
Dr. Jicheng Zhang, Dr. Li Liang, Dr. Weizhun Yang, Dr. Sherif Ramadan, Dr. Kedar Baryal, Dr. Chang-Xin Huo, Dr. Jamie J. Bernard, Dr. Jian Liu, Prof. Linda Hsieh-Wilson, Dr. Fuming Zhang, Prof. Robert J. Linhardt, Prof. Xuefei Huang
Affiliation:
Department of Chemistry, Michigan State University, East Lansing, MI 48824 USA
Department of Chemistry & Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180 USA
Chemistry Department, Faculty of Science, Benha University, Benha, Qaliobiya, 13518 Egypt
Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824 USA
Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 USA
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 USA
Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824 USA
Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824 USA
Description:
Heparan sulfate (HS) plays important roles in many biological processes. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of their structure-activity relationship. To facilitate biological studies, a new strategy has been developed to synthesize a HS-like pseudo-hexasaccharide library, where HS disaccharides were linked in a “head-to-tail” fashion from the reducing end of a disaccharide module to the non-reducing end of a neighboring module. Combinatorial syntheses of 27 HS-like pseudo-hexasaccharides were achieved. This new class of compounds bound with fibroblast growth factor 2 (FGF-2) with similar structure-activity trends as HS oligosaccharides bearing native glycosyl linkages. The ease of synthesis and the ability to mirror natural HS activity trends suggest that the new head-to-tail linked pseudo-oligosaccharides could be an exciting tool to facilitate the understanding of HS biology.
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