title: Divergent Synthesis of Chondroitin Sulfate Disaccharides and Identification of Sulfate Motifs that Inhibit Triple Negative Breast Cancer.
abstract: Glycosaminoglycans (GAGs) regulate many important physiological processes. A pertinent issue to address is whether GAGs encode important functional information via introduction of position specific sulfate groups in the GAG structure. However, procurement of pure, homogenous GAG motifs to probe the "sulfation code" is a challenging task due to isolation difficulty and structural complexity. To this end, we devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231.
authors.affiliation: Department of Chemistry, National University of Singapore (NUS), Singapore.|NUS Graduate School for Integrative Sciences and Engineering (NGS), Singapore.
authors.forename: Zhong Wei
authors.initials: ZW
authors.lastname: Poh
authors.affiliation: Department of Chemistry, National University of Singapore (NUS), Singapore.
authors.forename: Chin Heng
authors.initials: CH
authors.lastname: Gan
authors.affiliation: Department of Chemistry, National University of Singapore (NUS), Singapore.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, National University of Singapore (NUS), Singapore.
authors.forename: Suxian
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Anatomy, National University of Singapore (NUS), Singapore.
authors.forename: George W
authors.initials: GW
authors.lastname: Yip
authors.affiliation: Department of Chemistry, National University of Singapore (NUS), Singapore.|NUS Graduate School for Integrative Sciences and Engineering (NGS), Singapore.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Lam
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000138:chemical synthesis* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D015394:Molecular Structure; D064726:Triple Negative Breast Neoplasms
chemical_list: D000970:Antineoplastic Agents; D002809:Chondroitin Sulfates; D053148:Caspase 3; D053179:Caspase 7