Chemoenzymatic Synthesis of Homogeneous Heparan Sulfate and Chondroitin Sulfate Chimeras
Authors:
Eduardo Stancanelli, Wei Liu, Rylee Wander, Jine Li, Zhangjie Wang, Katelyn Arnold, Guowei Su, Adam Kanack, Truong Quang Pham, Vijayakanth Pagadala, Anand Padmanabhan, Yongmei Xu, Jian Liu*
Affiliation:
Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, PR China
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Glycan Therapeutics, 617 Hutton Street, Raleigh, North Carolina 27606, United States
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55904, United States
Description:
Heparan sulfate (HS) and chondroitin sulfate (CS) are two structurally distinct natural polysaccharides. Here, we report the synthesis of a library of seven structurally homogeneous HS and CS chimeric dodecasaccharides (12-mers). The synthesis was accomplished using six HS biosynthetic enzymes and four CS biosynthetic enzymes. The chimeras contain a CS domain on the reducing end and a HS domain on the nonreducing end. The synthesized chimeras display anticoagulant activity as measured by both in vitro and ex vivo experiments. Furthermore, the anticoagulant activity of H/C 12-mer 5 is reversible by protamine, a U.S. Food and Drug Administration-approved polypeptide to neutralize anticoagulant drug heparin. Our findings demonstrate the synthesis of unnatural HS-CS chimeric oligosaccharides using natural biosynthetic enzymes, offering a new class of glycan molecules for biological research.
Publications:
- Stancanelli, Eduardo, Wei Liu, Rylee Wander, Jine Li, Zhangjie Wang, Katelyn Arnold, Guowei Su et al.; Chemoenzymatic synthesis of homogeneous heparan sulfate and chondroitin sulfate chimeras.; ACS chemical biology, 2022
Tags:
Heparan sulfate Oligosaccharides Peptides and proteinsRelated Projects:
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