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dc.contributor.authorDussouy, C
dc.contributor.authorKishor, C
dc.contributor.authorLambert, A
dc.contributor.authorLamoureux, C
dc.contributor.authorBlanchard, H
dc.contributor.authorGrandjean, C
dc.date.accessioned2020-08-04T00:00:22Z
dc.date.available2020-08-04T00:00:22Z
dc.date.issued2020
dc.identifier.issn1747-0277
dc.identifier.doi10.1111/cbdd.13683
dc.identifier.urihttp://hdl.handle.net/10072/396120
dc.description.abstractGalectins play key roles in numerous biological processes. Their mode of action depends on their localization which can be extracellular, cytoplasmic, or nuclear and is partly mediated through interactions with β-galactose containing glycans. Galectins have emerged as novel therapeutic targets notably for the treatment of inflammatory disorders and cancers. This has stimulated the design of carbohydrate-based inhibitors targeting the carbohydrate recognition domains (CRDs) of the galectins. Pursuing this approach, we reasoned that linear oligogalactosides obtained by straightforward iterative click chemistry could mimic poly-lactosamine motifs expressed at eukaryote cell surfaces which the extracellular form of galectin-3, a prominent member of the galectin family, specifically recognizes. Affinities toward galectin-3 consistently increased with the length of the representative oligogalactosides but without reaching that of oligo-lactosamines. Elucidation of the X-ray crystal structures of the galectin-3 CRD in complex with a synthesized di- and tri-galactoside confirmed that the compounds bind within the carbohydrate-binding site. The atomic structures revealed that binding interactions mainly occur with the galactose moiety at the non-reducing end, primarily with subsites C and D of the CRD, differing from oligo-lactosamine which bind more consistently across the whole groove formed by the five subsites (A-E) of the galectin-3 CRD.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofjournalChemical Biology and Drug Design
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchcode0601
dc.subject.keywords1,2,3-triazole
dc.subject.keywordsX-ray crystallography
dc.subject.keywordscarbohydrate mimetics
dc.subject.keywordsgalectin
dc.subject.keywordsgalectin-3 inhibitor
dc.titleLinear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationDussouy, C; Kishor, C; Lambert, A; Lamoureux, C; Blanchard, H; Grandjean, C, Linear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development, Chemical Biology and Drug Design, 2020
dc.date.updated2020-08-03T23:57:48Z
dc.description.versionAccepted Manuscript (AM)
gro.description.notepublicThis publication has been entered in Griffith Research Online as an advanced online version.
gro.rights.copyright© 2020 John Wiley & Sons A/S. This is the peer reviewed version of the following article: Linear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development, Chemical Biology and Drug Design, 2020, which has been published in final form at https://doi.org/10.1111/cbdd.13683. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)
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gro.griffith.authorBlanchard, Helen


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