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Immunogenic Sulfated l-Idose Homo Oligosaccharides Elicit Neutralizing Antibody against Native Heparan Sulfate with Biomarker and Therapeutic Possibilities

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dc.contributor.author VISHWESHWARA, SHARATH S. en_US
dc.contributor.author BHOGE, PREETI RAVINDRA en_US
dc.contributor.author ANAND, SAURABH en_US
dc.contributor.author RAIGAWALI, RAKESH en_US
dc.contributor.author CHANDRA, ANKITA en_US
dc.contributor.author Saladi, Srinivas Vinod en_US
dc.contributor.author KIKKERI, RAGHAVENDRA en_US
dc.date.accessioned 2024-10-29T06:44:40Z
dc.date.available 2024-10-29T06:44:40Z
dc.date.issued 2024-10 en_US
dc.identifier.citation Journal of Medicinal Chemistry, 67(20), 18465–18477. en_US
dc.identifier.issn 0022-2623 en_US
dc.identifier.issn 1520-4804 en_US
dc.identifier.uri https://doi.org/10.1021/acs.jmedchem.4c01772 en_US
dc.identifier.uri http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/9147
dc.description.abstract Heparan sulfate (HS) is a non-immunogenic antigen, and developing antibodies against specific sulfated patterns in HS poses significant challenges. Herein, we employed an innovative immunization strategy that exploits the molecular mimicry of HS to generate antibodies against HS sequences. Mice were immunized with synthetic sulfated oligo-l-idose (ID49) that mimics optimum 67% of the conserved structure of HS ligands. This immunization of ID49@CRM197 with alum and Freund’s adjuvant resulted in the production of robust IgG antibody responses targeting ID49 and cross-reactivity with the N-sulfated HS ligands compared to N-unsubstituted and N-acetate domain synthetic HS ligands. Such a pharmacological agent exhibited distinct staining of tissue sections and cell lines and induced complement-dependent cell cytotoxicity against SK-BR-3 cancer cells. Moreover, these antibodies inhibited heparin-mediated anticoagulation activity similar to that of protamine. These findings highlight the biomarker and possible therapeutic capability of the antibodies. en_US
dc.language.iso en en_US
dc.publisher American Chemical Society en_US
dc.subject Biopolymers en_US
dc.subject Immunology en_US
dc.subject Ligands en_US
dc.subject Mixtures en_US
dc.subject Peptides and proteins en_US
dc.subject 2024 en_US
dc.subject 2024-OCT-WEEK2 en_US
dc.subject TOC-OCT-2024  en_US
dc.title Immunogenic Sulfated l-Idose Homo Oligosaccharides Elicit Neutralizing Antibody against Native Heparan Sulfate with Biomarker and Therapeutic Possibilities en_US
dc.type Article en_US
dc.contributor.department Dept. of Chemistry en_US
dc.identifier.sourcetitle Journal of Medicinal Chemistry en_US
dc.publication.originofpublisher Foreign en_US


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