{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:49:03Z","timestamp":1792079343640,"version":"4.4.0"},"reference-count":33,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["AG087305"],"award-info":[{"award-number":["AG087305"]}]},{"name":"National Institutes of Health (NIH)","award":["GM148100"],"award-info":[{"award-number":["GM148100"]}]},{"name":"National Institutes of Health (NIH)","award":["HL139187"],"award-info":[{"award-number":["HL139187"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dermatan sulfate epimerase 1 (DS-epi1, DSE) and dermatan sulfate 4-O-sulfotransferase (DS 4-OST, CHST14) are critical enzymes involved in the biosynthesis of dermatan sulfate. In this study, structurally homogeneous chondroitin oligosaccharide substrates were used to investigate the substrate specificity of each individual enzyme, as well as their combined actions. The structures of the enzyme-modified oligosaccharides were confirmed by high-resolution mass spectrometry (MS) and NMR or determined by LC\u2013MS-based sequencing analysis. Our results demonstrate that DS-epi1 catalyzes the reversible conversion between glucuronic acid (GlcA) and iduronic acid (IdoA), with GlcA being the predominant product once the reaction reaches equilibrium. DS 4-OST selectively sulfates the 4-hydroxyl group of N-acetylgalactosamine (GalNAc) residues that are linked to the reducing end of an IdoA unit (\u2013IdoA\u2013GalNAc\u2013). Furthermore, DS-epi1 and DS 4-OST act in a concerted and ordered manner to generate clustered \u2013IdoA\u2013GalNAc4S\u2013 domains. During the reaction, the enzyme mixture initiates modifications at the non-reducing end of the saccharide chain and proceeds toward the reducing end consecutively. These findings provide new insights into the regulatory mechanisms governing dermatan sulfate biosynthesis and demonstrate the feasibility of synthesizing structurally defined dermatan sulfate oligosaccharides.<\/jats:p>","DOI":"10.1021\/acschembio.6c00533","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:11:21Z","timestamp":1788405081000},"page":"2415-2426","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the Substrate Specificities of Dermatan Sulfate Epimerase 1 (DS-epi1) and 4-\n                    <i>O<\/i>\n                    -sulfotransferase (DS 4-OST) Using Synthetic Oligosaccharide Substrates"],"prefix":"10.1021","volume":"21","author":[{"given":"Yongmei","family":"Xu","sequence":"first","affiliation":[{"name":"University of North Carolina , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chi","family":"Wang","sequence":"additional","affiliation":[{"name":"University of North Carolina , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Stancanelli","sequence":"additional","affiliation":[{"name":"Glycan Therapeutics , , ,","place":["Raleigh, North Carolina, United States, 27606"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Wang","sequence":"additional","affiliation":[{"name":"University of North Carolina , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of North Carolina , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-9831","authenticated-orcid":true,"given":"Emil","family":"Tykesson","sequence":"additional","affiliation":[{"name":"Lund University , , ,","place":["Lund, Sweden, SE-221 00"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Lund University , , ,","place":["Lund, Sweden, SE-221 00"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8552-1400","authenticated-orcid":true,"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"University of North Carolina , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"2026101511072439800_cit1","doi-asserted-by":"publisher","first-page":"117R","DOI":"10.1093\/glycob\/cwf066","article-title":"Dermatan sulfate: new functions from an old glycosaminoglycan","volume":"12","author":"Trowbridge","year":"2002","journal-title":"Glycobiology"},{"key":"2026101511072439800_cit2","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1093\/glycob\/cwz019","article-title":"Recombinant dermatan sulfate is a potent activator of heparin cofactor II-dependent inhibition of thrombin","volume":"29","author":"Tykesson","year":"2019","journal-title":"Glycobiology"},{"key":"2026101511072439800_cit3","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41556-026-01879-y","article-title":"Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis","volume":"28","author":"B\u00e5ng-Rudenstam","year":"2026","journal-title":"Nat. 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