{"entity": "researcher", "timestamp": "2026-08-22T06:57:51.983Z", "family": "Maccarana", "given": "Marco", "initials": "M", "orcid": "0000-0003-3549-8921", "affiliations": ["Department of Medical Biochemistry and Microbiology, University of Uppsala, Husargatan 3, 75123, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca8e408602c742478ab42e041504eb38.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca8e408602c742478ab42e041504eb38"}}, "publications": [{"entity": "publication", "iuid": "c91ecd53381846a3aa62a6b266b7b410", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c91ecd53381846a3aa62a6b266b7b410.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c91ecd53381846a3aa62a6b266b7b410"}}, "title": "Inhibitors of dermatan sulfate epimerase 1 decreased accumulation of glycosaminoglycans in mucopolysaccharidosis type I fibroblasts.", "authors": [{"family": "Maccarana", "given": "Marco", "initials": "M", "orcid": "0000-0003-3549-8921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca8e408602c742478ab42e041504eb38.json"}}, {"family": "Li", "given": "Binjie", "initials": "B", "orcid": "0000-0003-4058-180X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b9474621a26f49558f430c91d61fce07.json"}}, {"family": "Li", "given": "Honglian", "initials": "H", "orcid": "0000-0002-5820-3121", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7a3ac57ba039433b8eacad4504af66fd.json"}}, {"family": "Fang", "given": "Jianping", "initials": "J", "orcid": "0000-0002-1695-2693", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19a0d0b14f1f4fd7afbc007555207b5c.json"}}, {"family": "Yu", "given": "Mingjia", "initials": "M", "orcid": "0000-0002-8906-7476", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e7da2d9779f41e68ad8e99ab4874812.json"}}, {"family": "Li", "given": "Jin-Ping", "initials": "JP", "orcid": "0000-0002-4255-3581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ab4d6e3d5eb4551a1cc622b5917dc3b.json"}}], "type": "journal article", "published": "2024-04-24", "journal": {"title": "Glycobiology", "issn": "1460-2423", "volume": "34", "issue": "6", "issn-l": "0959-6658"}, "abstract": "Genetic deficiency of alpha-L-iduronidase causes mucopolysaccharidosis type I (MPS-I) disease, due to accumulation of glycosaminoglycans (GAGs) including chondroitin/dermatan sulfate (CS/DS) and heparan sulfate (HS) in cells. Currently, patients are treated by infusion of recombinant iduronidase or by hematopoietic stem cell transplantation. An alternative approach is to reduce the L-iduronidase substrate, through limiting the biosynthesis of iduronic acid. Our earlier study demonstrated that ebselen attenuated GAGs accumulation in MPS-I cells, through inhibiting iduronic acid producing enzymes. However, ebselen has multiple pharmacological effects, which prevents its application for MPS-I. Thus, we continued the study by looking for novel inhibitors of dermatan sulfate epimerase 1 (DS-epi1), the main responsible enzyme for production of iduronic acid in CS/DS chains. Based on virtual screening of chemicals towards chondroitinase AC, we constructed a library with 1,064 compounds that were tested for DS-epi1 inhibition. Seventeen compounds were identified to be able to inhibit 27%-86% of DS-epi1 activity at 10 \u03bcM. Two compounds were selected for further investigation based on the structure properties. The results show that both inhibitors had a comparable level in inhibition of DS-epi1while they had negligible effect on HS epimerase. The two inhibitors were able to reduce iduronic acid biosynthesis in CS/DS and GAG accumulation in WT and MPS-I fibroblasts. Docking of the inhibitors into DS-epi1 structure shows high affinity binding of both compounds to the active site. The collected data indicate that these hit compounds may be further elaborated to a potential lead drug used for attenuation of GAGs accumulation in MPS-I patients.", "doi": "10.1093/glycob/cwae025", "pmid": "38760939", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11101759"}, {"db": "pii", "key": "7676076"}], "notes": [], "created": "2026-08-21T12:08:53.529Z", "modified": "2026-08-21T12:08:53.804Z"}, {"entity": "publication", "iuid": "b75d398b04f44b6b8e95d6ee8e51cbe2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b75d398b04f44b6b8e95d6ee8e51cbe2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b75d398b04f44b6b8e95d6ee8e51cbe2"}}, "title": "Implications of Heparanase on Heparin Synthesis and Metabolism in Mast Cells.", "authors": [{"family": "Maccarana", "given": "Marco", "initials": "M", "orcid": "0000-0003-3549-8921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca8e408602c742478ab42e041504eb38.json"}}, {"family": "Jia", "given": "Juan", "initials": "J"}, {"family": "Li", "given": "Honglian", "initials": "H"}, {"family": "Zhang", "given": "Xiao", "initials": "X"}, {"family": "Vlodavsky", "given": "Israel", "initials": "I"}, {"family": "Li", "given": "Jin-Ping", "initials": "JP"}], "type": "journal article", "published": "2022-04-27", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "23", "issue": "9", "issn-l": null}, "abstract": "Heparin is a polysaccharide expressed in animal connective tissue-type mast cells. Owing to the special pentasaccharide sequence, heparin specifically binds to antithrombin (AT) and increases the inhibitory activity of AT towards coagulation enzymes. Heparin isolated from porcine intestinal mucosa has an average molecular weight of 15 kDa, while heparins recovered from rat skin and the peritoneal cavity were 60-100 kDa and can be fragmented by the endo-glucuronidase heparanase in vitro. In this study, we have examined heparin isolated from in vitro matured fetal skin mast cells (FSMC) and peritoneal cavity mast cells (PCMC) collected from wildtype (WT), heparanase knockout (Hpa-KO), and heparanase overexpressing (Hpa-tg) mice. The metabolically 35S-labeled heparin products from the mast cells of WT, Hpa-KO, and Hpa-tg mice were compared and analyzed for molecular size and AT-binding activity. The results show that PCMC produced heparins with a size similar to heparin from porcine intestinal mast cells, whilst FSMC produced much longer chains. As expected, heparanase overexpression resulted in the generation of smaller fragments in both cell types, while heparins recovered from heparanase knockout cells were slightly longer than heparin from WT cells. Unexpectedly, we found that heparanase expression affected the production of total glycosaminoglycans (GAGs) and the proportion between heparin and other GAGs but essentially had no effect on heparin catabolism.", "doi": "10.3390/ijms23094821", "pmid": "35563215", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9102752"}, {"db": "pii", "key": "ijms23094821"}], "notes": [], "created": "2026-08-21T13:03:29.446Z", "modified": "2026-08-21T13:03:29.507Z"}]}