title: Irreversible heavy chain transfer to chondroitin.
abstract: We have recently demonstrated that the transfer of heavy chains (HCs) from inter-α-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture.
authors.affiliation: From the Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195 and lauerm1@ccf.org.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lauer
authors.affiliation: From the Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195 and.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
authors.affiliation: the Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126.
authors.forename: Dixy E
authors.initials: DE
authors.lastname: Green
authors.affiliation: the Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126.
authors.forename: Paul L
authors.initials: PL
authors.lastname: DeAngelis
authors.affiliation: From the Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195 and.
authors.forename: Anthony
authors.initials: A
authors.lastname: Calabro
mesh_terms: D000464:Alginates / Q000737:chemistry; D000510:Alpha-Globulins / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000737:chemistry; D002807:Chondroitin / Q000737:chemistry*; D002809:Chondroitin Sulfates / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007700:Kinetics; D009844:Oligosaccharides / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D000464:Alginates; D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; D002807:Chondroitin; D002809:Chondroitin Sulfates; D004187:Disaccharides; D020723:Glucuronic Acid; D006497:Heparan Sulfate; D006603:Hexuronic Acids; D006820:Hyaluronic Acid; D009844:Oligosaccharides; C072273:TNFAIP6 protein, human; C560363:heparosan; C011877:inter-alpha-inhibitor
keywords: Chondroitin; Chondroitin Sulfate; Glycosaminoglycan; Heparan Sulfate; Hyaluronan