Solid-Phase-Supported Chemoenzymatic Synthesis and Analysis of Chondroitin Sulfate Proteoglycan Glycopeptides.

Autor: Lin PH; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States.; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan, 48824, United States., Xu Y; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599, United States., Bali SK; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States., Kim J; Department of Chemistry, University of Georgia, Athens, GA 30602, United States., Gimeno A; Chemical Glycobiology Lab, Center for Cooperative Research in Biosciences (CICbioGUNE), Basque Research and Technology Alliance (BRTA), 48160, Derio, Bizkaia, Spain.; Ikerbasque, Basque Foundation for Science, Bilbao, 48009, Spain., Roberts ET; Department of Chemistry, University of Georgia, Athens, GA 30602, United States., James D; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States., Almeida NMS; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States., Loganathan N; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States., Fan F; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States.; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan, 48824, United States., Wilson AK; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States., Jonathan Amster I; Department of Chemistry, University of Georgia, Athens, GA 30602, United States., Moremen KW; Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, United States.; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, United States., Liu J; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599, United States., Jiménez-Barbero J; Chemical Glycobiology Lab, Center for Cooperative Research in Biosciences (CICbioGUNE), Basque Research and Technology Alliance (BRTA), 48160, Derio, Bizkaia, Spain.; Ikerbasque, Basque Foundation for Science, Bilbao, 48009, Spain.; Department of Inorganic & Organic Chemistry, Faculty of Science and Technology, University of the Basque Country, EHU-UPV, Leioa, 48940, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, 28029, Spain., Huang X; Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824, United States.; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan, 48824, United States.; Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan, 48824, United States.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Aug 19; Vol. 63 (34), pp. e202405671. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1002/anie.202405671
Abstrakt: Proteoglycans (PGs), consisting of glycosaminoglycans (GAGs) linked with the core protein through a tetrasaccharide linkage region, play roles in many important biological events. The chemical synthesis of PG glycopeptides is extremely challenging. In this work, the enzymes required for synthesis of chondroitin sulfate (CS) PG (CSPG) have been expressed and the suitable sequence of enzymatic reactions has been established. To expedite CSPG synthesis, the peptide acceptor was immobilized on solid phase and the glycan units were directly installed enzymatically onto the peptide. Subsequent enzymatic chain elongation and sulfation led to the successful synthesis of CSPG glycopeptides. The CS dodecasaccharide glycopeptide was the longest homogeneous CS glycopeptide synthesized to date. The enzymatic synthesis was much more efficient than the chemical synthesis of the corresponding CS glycopeptides, which could reduce the total number of synthetic steps by 80 %. The structures of the CS glycopeptides were confirmed by mass spectrometry analysis and NMR studies. In addition, the interactions between the CS glycopeptides and cathepsin G were studied. The sulfation of glycan chain was found to be important for binding with cathepsin G. This efficient chemoenzymatic strategy opens new avenues to investigate the structures and functions of PGs.
(© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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