{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:44:23Z","timestamp":1792784663131,"version":"4.5.0"},"reference-count":52,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100020769","name":"National Institute of Metrology, China","doi-asserted-by":"publisher","award":["AKYCX2513"],"award-info":[{"award-number":["AKYCX2513"]}],"id":[{"id":"10.13039\/501100020769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020769","name":"National Institute of Metrology, China","doi-asserted-by":"publisher","award":["APT2602-1"],"award-info":[{"award-number":["APT2602-1"]}],"id":[{"id":"10.13039\/501100020769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012538","name":"Swedish Cancer Foundation","doi-asserted-by":"publisher","award":["24 3505 Pj"],"award-info":[{"award-number":["24 3505 Pj"]}],"id":[{"id":"10.13039\/100012538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005085","name":"Beijing Institute of Technology","doi-asserted-by":"publisher","award":["3100012222222"],"award-info":[{"award-number":["3100012222222"]}],"id":[{"id":"10.13039\/501100005085","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Administration for Market Regulation","award":["AKYKF2417"],"award-info":[{"award-number":["AKYKF2417"]}],"id":[{"id":"https:\/\/ror.org\/00aaqtw69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"State Administration for Market Regulation","award":["AKYKF2507"],"award-info":[{"award-number":["AKYKF2507"]}],"id":[{"id":"https:\/\/ror.org\/00aaqtw69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Basic Research Program of China (973 Program)","award":["2023YFA0914300"],"award-info":[{"award-number":["2023YFA0914300"]}]},{"name":"Swedish Research Council (VR)","award":["2024-02661"],"award-info":[{"award-number":["2024-02661"]}],"id":[{"id":"https:\/\/ror.org\/03zttf063","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["32201053"],"award-info":[{"award-number":["32201053"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"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>Heparanase (Hpse) is an endo-\u03b2-glucuronidase that specifically cleaves heparan sulfate (HS) and plays critical roles in the pathogenesis of multiple diseases, making it a well-validated therapeutic target. To identify novel Hpse inhibitors, we developed a rule-based computational pipeline to construct a rigorously curated database of HS oligosaccharides ranging from disaccharides to hexasaccharides. This database systematically encompasses all possible sulfation patterns and stereochemical configurations of the three monosaccharide species in HS. Using a multistage virtual screening strategy against Hpse, we prioritized high-affinity HS oligosaccharides for detailed analysis. Structural motif profiling of the top-ranking candidates revealed that even-numbered oligosaccharides preferentially retain the iduronic acid (IdoA)-N-acetyl-3-O-sulfated glucosamine (GlcNAc3S) motif, whereas odd-numbered species are enriched with IdoA2S and 3,6-O-sulfated glucosamine (GlcN3S6S) motifs. Systematic desulfation of the lead compound, HP-dp5R1, found that removal of 2-O- or 3-O-sulfate groups resulted in substantially larger penalties to binding-free energy compared with removal of 6-O- or N-sulfates, indicating a dominant role for 2-O\/3-O sulfation in Hpse recognition. Molecular dynamics simulations and binding-free energy calculations further revealed that longer oligosaccharides form extensive interactions with the heparin-binding domains (HBD1 and HBD2) flanking the catalytic cleft, leading to reduced conformational fluctuation. Together with preliminary experimental results using selected octasaccharides that resemble the structural features of the top-hit oligosaccharides identified from virtual screening, we demonstrate that the integrated computational platform provides a robust foundation for the rational design of HS-based Hpse inhibitors. More broadly, the virtual HS oligosaccharide database described here is expected to serve as a powerful resource for screening other HS-binding proteins and for the discovery of novel agonists or antagonists.<\/jats:p>","DOI":"10.1021\/acschembio.6c00454","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:01:57Z","timestamp":1786600917000},"page":"2286-2297","source":"Crossref","is-referenced-by-count":1,"title":["Systematic Virtual Screening of Heparan Sulfate Oligosaccharides and Mechanistic Insights into Heparanase Inhibition"],"prefix":"10.1021","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-180X","authenticated-orcid":true,"given":"Binjie","family":"Li","sequence":"first","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siran","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Institute of Metrology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonglin","family":"Lan","sequence":"additional","affiliation":[{"name":"Uppsala University , , ,","place":["Uppsala, Sweden, 75105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3549-8921","authenticated-orcid":true,"given":"Marco","family":"Maccarana","sequence":"additional","affiliation":[{"name":"Uppsala University , , ,","place":["Uppsala, Sweden, 75105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Uppsala University , , ,","place":["Uppsala, Sweden, 75105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-2550","authenticated-orcid":true,"given":"Vito","family":"Ferro","sequence":"additional","affiliation":[{"name":"The University of Queensland , , , ,","place":["Brisbane, QLD, Australia, 4072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Cao","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianji","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Institute of Metrology , , ,","place":["Beijing, China, 100029"]},{"name":"Key Laboratory of Chemical Metrology and Applications on Nutrition and Health for State Market Regulation , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-7476","authenticated-orcid":true,"given":"Mingjia","family":"Yu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Technology , , ,","place":["Beijing, China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-3581","authenticated-orcid":true,"given":"Jin-Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]},{"name":"Uppsala University , , ,","place":["Uppsala, Sweden, 75105"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"issue":"6","key":"2026101511072422600_cit1","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1093\/glycob\/cww003","article-title":"Kinetic Analysis and Molecular Modeling of the Inhibition Mechanism of Roneparstat (SST0001) on Human Heparanase","volume":"26","author":"Pala","year":"2016","journal-title":"Glycobiology"},{"issue":"1","key":"2026101511072422600_cit2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1093\/glycob\/cwr095","article-title":"Computational Analyses of the Catalytic and Heparin-Binding Sites and Their Interactions with Glycosaminoglycans in Glycoside Hydrolase Family 79 Endo-\u03b2-d-Glucuronidase (Heparanase)","volume":"22","author":"Gandhi","year":"2012","journal-title":"Glycobiology"},{"issue":"12","key":"2026101511072422600_cit3","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1038\/nchembio.1956","article-title":"Functional and Structural Characterization of a Heparanase","volume":"11","author":"Bohlmann","year":"2015","journal-title":"Nat. Chem. Biol."},{"issue":"4","key":"2026101511072422600_cit4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005181","article-title":"Newly Generated Heparanase Knock-Out Mice Unravel Co-Regulation of Heparanase and Matrix Metalloproteinases","volume":"4","author":"Zcharia","year":"2009","journal-title":"PLoS One"},{"key":"2026101511072422600_cit5","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.drup.2016.10.001","article-title":"Heparanase: From Basic Research to Therapeutic Applications in Cancer and Inflammation","volume":"29","author":"Vlodavsky","year":"2016","journal-title":"Drug Resist. Updat."},{"issue":"18","key":"2026101511072422600_cit6","doi-asserted-by":"publisher","first-page":"6473","DOI":"10.1073\/pnas.0502287102","article-title":"In Vivo Fragmentation of Heparan Sulfate by Heparanase Overexpression Renders Mice Resistant to Amyloid Protein A Amyloidosis","volume":"102","author":"Li","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"12","key":"2026101511072422600_cit7","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/nchembio.2007.41","article-title":"Transgenic or Tumor-Induced Expression of Heparanase Upregulates Sulfation of Heparan Sulfate","volume":"3","author":"Escobar Galvis","year":"2007","journal-title":"Nat. Chem. Biol."},{"issue":"3","key":"2026101511072422600_cit8","doi-asserted-by":"publisher","DOI":"10.3390\/cells13030211","article-title":"A New Synthesized Dicarboxylated Oxy-Heparin Efficiently Attenuates Tumor Growth and Metastasis","volume":"13","author":"Li","year":"2024","journal-title":"Cells"},{"issue":"1","key":"2026101511072422600_cit9","doi-asserted-by":"publisher","DOI":"10.1038\/srep46229","article-title":"Overexpression of Heparanase Enhances T Lymphocyte Activities and Intensifies the Inflammatory Response in a Model of Murine Rheumatoid Arthritis","volume":"7","author":"Digre","year":"2017","journal-title":"Sci. Rep."},{"issue":"6","key":"2026101511072422600_cit10","doi-asserted-by":"publisher","first-page":"647","DOI":"10.4155\/fmc-2016-0012","article-title":"Heparanase: A Rainbow Pharmacological Target Associated to Multiple Pathologies Including Rare Diseases","volume":"8","author":"Rivara","year":"2016","journal-title":"Future Med. Chem."},{"issue":"10","key":"2026101511072422600_cit11","doi-asserted-by":"publisher","first-page":"e469","DOI":"10.3324\/haematol.2017.182865","article-title":"Phase I Study of the Heparanase Inhibitor Roneparstat: An Innovative Approach for Ultiple Myeloma Therapy","volume":"103","author":"Galli","year":"2018","journal-title":"Haematologica"},{"issue":"2","key":"2026101511072422600_cit12","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1158\/1535-7163.MCT-18-0417","article-title":"Necuparanib, A Multitargeting Heparan Sulfate Mimetic, Targets Tumor and Stromal Compartments in Pancreatic Cancer","volume":"18","author":"MacDonald","year":"2019","journal-title":"Mol. Cancer Ther."},{"issue":"32","key":"2026101511072422600_cit13","doi-asserted-by":"publisher","first-page":"11384","DOI":"10.3748\/wjg.v20.i32.11384","article-title":"Adjuvant Heparanase Inhibitor PI-88 Therapy for Hepatocellular Carcinoma Recurrence","volume":"20","author":"Liu","year":"2014","journal-title":"World J. Gastroenterol."},{"issue":"8","key":"2026101511072422600_cit14","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/s41416-018-0006-0","article-title":"A Phase I Study of the Novel Immunomodulatory Agent PG545 (Pixatimod) in Subjects with Advanced Solid Tumours","volume":"118","author":"Dredge","year":"2018","journal-title":"Br. J. Cancer"},{"issue":"3","key":"2026101511072422600_cit15","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1083\/jcb.200604035","article-title":"Interactions between Heparan Sulfate and Proteins: The Concept of Specificity","volume":"174","author":"Kreuger","year":"2006","journal-title":"J. Cell Biol."},{"key":"2026101511072422600_cit16","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/978-3-030-34521-1_2","article-title":"Heparanase - Discovery and Targets","volume":"1221","author":"Lindahl","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"issue":"30","key":"2026101511072422600_cit17","doi-asserted-by":"publisher","first-page":"18770","DOI":"10.1074\/jbc.273.30.18770","article-title":"Substrate Specificity of Heparanases from Human Hepatoma and Platelets*","volume":"273","author":"Pikas","year":"1998","journal-title":"J. Biol. Chem."},{"issue":"45","key":"2026101511072422600_cit18","doi-asserted-by":"publisher","first-page":"42488","DOI":"10.1074\/jbc.M206510200","article-title":"Structural Recognition by Recombinant Human Heparanase That Plays Critical Roles in Tumor Metastasis: HIERARCHICAL SULFATE GROUPS WITH DIFFERENTIAL EFFECTS AND THE ESSENTIAL TARGET DISULFATED TRISACCHARIDE SEQUENCE*","volume":"277","author":"Okada","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"19","key":"2026101511072422600_cit19","doi-asserted-by":"publisher","first-page":"14504","DOI":"10.1074\/jbc.M110.104166","article-title":"Unraveling the Specificity of Heparanase Utilizing Synthetic Substrates","volume":"285","author":"Peterson","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"11","key":"2026101511072422600_cit20","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23112971","article-title":"The Development of Assays for Heparanase Enzymatic Activity: Towards a Gold Standard","volume":"23","author":"Chhabra","year":"2018","journal-title":"Molecules"},{"issue":"41","key":"2026101511072422600_cit21","doi-asserted-by":"publisher","first-page":"34836","DOI":"10.1074\/jbc.M112.390161","article-title":"Deciphering Mode of Action of Heparanase Using Structurally Defined Oligosaccharides*","volume":"287","author":"Peterson","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"5","key":"2026101511072422600_cit22","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.matbio.2013.02.006","article-title":"Multi-Faceted Substrate Specificity of Heparanase","volume":"32","author":"Peterson","year":"2013","journal-title":"Matrix Biol."},{"key":"2026101511072422600_cit23","volume-title":"Protein Preparation Wizard","author":"Schr\u00f6dinger Release 2018-1","year":"2018"},{"issue":"3","key":"2026101511072422600_cit24","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments","volume":"27","author":"Madhavi Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"2026101511072422600_cit25","volume-title":"Maestro","author":"Schr\u00f6dinger Release 2018-1","year":"2018"},{"issue":"12","key":"2026101511072422600_cit26","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/nsmb.3136","article-title":"Structural Characterization of Human Heparanase Reveals Insights into Substrate Recognition","volume":"22","author":"Wu","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"issue":"1","key":"2026101511072422600_cit27","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins","volume":"12","author":"Harder","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"2026101511072422600_cit28","volume-title":"LigPrep","author":"Schr\u00f6dinger Release 2018-1","year":"2018"},{"key":"2026101511072422600_cit29","volume-title":"Epik","author":"Schr\u00f6dinger Release 2018-1","year":"2018"},{"key":"2026101511072422600_cit30","volume-title":"Glide","author":"Schr\u00f6dinger Release 2018-1","year":"2018"},{"issue":"7","key":"2026101511072422600_cit31","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2 Enrichment Factors in Database Screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"issue":"7","key":"2026101511072422600_cit32","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1 Method and Assessment of Docking Accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"issue":"11","key":"2026101511072422600_cit33","doi-asserted-by":"publisher","first-page":"7106","DOI":"10.1021\/acs.jctc.1c00810","article-title":"Efficient Exploration of Chemical Space with Docking and Deep Learning","volume":"17","author":"Yang","year":"2021","journal-title":"J. Chem. Theory Comput."},{"issue":"21","key":"2026101511072422600_cit34","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein\u2212Ligand Complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"issue":"1","key":"2026101511072422600_cit35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-64480-1","article-title":"Inhibition of PGK1 Ameliorates Acute Kidney Injury through Inactivating the PKM2\/ALOX12\/Ferroptosis Pathway in a Study with Male Mice","volume":"16","author":"Zhu","year":"2025","journal-title":"Nat. Commun."},{"key":"2026101511072422600_cit36","author":"Schr\u00f6dinger Release 2018-1","year":"2018","journal-title":"Prime"},{"issue":"10","key":"2026101511072422600_cit37","doi-asserted-by":"publisher","first-page":"2794","DOI":"10.1002\/prot.23106","article-title":"The VSGB 20 Model: A next Generation Energy Model for High Resolution Protein Structure Modeling","volume":"79","author":"Li","year":"2011","journal-title":"Proteins: Struct., Funct., Bioinf."},{"issue":"1","key":"2026101511072422600_cit38","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0010-4655(95)00042-E","article-title":"GROMACS: A Message-Passing Parallel Molecular Dynamics Implementation","volume":"91","author":"Berendsen","year":"1995","journal-title":"Comput. Phys. Commun."},{"issue":"8","key":"2026101511072422600_cit39","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"2026101511072422600_cit40","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-5-367","article-title":"ACPYPE - AnteChamber PYthon Parser interfacE","volume":"5","author":"Sousa da Silva","year":"2012","journal-title":"BMC. Res. Notes"},{"key":"2026101511072422600_cit41","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"issue":"12","key":"2026101511072422600_cit42","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic Transitions in Single Crystals: A New Molecular Dynamics Method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"issue":"12","key":"2026101511072422600_cit43","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh Ewald: An N\u00b7log(N) Method for Ewald Sums in Large Systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"issue":"10","key":"2026101511072422600_cit44","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: Multiple Ligand-Protein Interaction Diagrams for Drug Discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"2026101511072422600_cit45","author":"Schr\u00f6dinger","year":"2026","journal-title":"The PyMOL Molecular Graphics System, Version 2.5"},{"key":"2026101511072422600_cit46","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2022.120191","article-title":"Interacting Polymer-Modification Enzymes in Heparan Sulfate Biosynthesis","volume":"299","author":"Zhang","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"2026101511072422600_cit47","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.chroma.2016.12.021","article-title":"Top-down and Bottom-up Analysis of Commercial Enoxaparins","volume":"1480","author":"Liu","year":"2017","journal-title":"J. Chromatogr. A"},{"issue":"7","key":"2026101511072422600_cit48","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202400633","article-title":"A Novel Series of Synthetic Heparin-Mimetics\u2212Itaconic Acid-Containing Copolymers for Targeting Tumor Cell Coagulability and Metastasis","volume":"25","author":"Nekipelov","year":"2025","journal-title":"Macromol. Biosci."},{"issue":"6","key":"2026101511072422600_cit49","doi-asserted-by":"publisher","first-page":"7080","DOI":"10.1021\/acsami.0c20744","article-title":"Inhibition of Tumor\u2212Host Cell Interactions Using Synthetic Heparin Mimetics","volume":"13","author":"Gockel","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026101511072422600_cit50","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1096\/fj.03-0572com","article-title":"Transgenic Expression of Mammalian Heparanase Uncovers Physiological Functions of Heparan Sulfate in Tissue Morphogenesis, Vascularization, and Feeding Behavior","volume":"18","author":"Zcharia","year":"2004","journal-title":"FASEB J."},{"issue":"8","key":"2026101511072422600_cit51","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1038\/nchembio.2395","article-title":"Activity-Based Probes for Functional Interrogation of Retaining \u03b2-Glucuronidases","volume":"13","author":"Wu","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"2026101511072422600_cit52","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2024.118052","article-title":"Synthetic Glycol-Split Heparin Tri- and Tetrasaccharides Provide New Insights into Structural Peculiarities for Antiheparanase Activity","volume":"118","author":"Ni","year":"2025","journal-title":"Bioorg. Med. Chem."}],"container-title":["ACS Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acschembio.6c00454","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/21\/9\/2286\/66521613\/cb-2026-00454m.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/21\/9\/2286\/66521613\/cb-2026-00454m.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:49:36Z","timestamp":1792079376000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acbcct\/article\/21\/9\/2286\/5254066\/Systematic-Virtual-Screening-of-Heparan-Sulfate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,8,13]]},"published-print":{"date-parts":[[2026,9,18]]}},"URL":"https:\/\/doi.org\/10.1021\/acschembio.6c00454","relation":{},"ISSN":["1554-8929","1554-8937"],"issn-type":[{"value":"1554-8929","type":"print"},{"value":"1554-8937","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}