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dc.contributor.authorBum-Erdene, Khuchtumur
dc.contributor.authorGagarinov, Ivan A
dc.contributor.authorCollins, Patrick M
dc.contributor.authorWinger, Moritz
dc.contributor.authorPearson, Andrew G
dc.contributor.authorWilson, Jennifer C
dc.contributor.authorLeffler, Hakon
dc.contributor.authorNilsson, Ulf J
dc.contributor.authorGrice, I Darren
dc.contributor.authorBlanchard, Helen
dc.date.accessioned2017-05-03T14:15:07Z
dc.date.available2017-05-03T14:15:07Z
dc.date.issued2013
dc.date.modified2014-01-30T22:09:43Z
dc.identifier.issn1439-4227
dc.identifier.doi10.1002/cbic.201300245
dc.identifier.urihttp://hdl.handle.net/10072/56214
dc.description.abstractGalectin-3 is extensively involved in metabolic and disease processes, such as cancer metastasis, thus giving impetus for the design of specific inhibitors targeting this b-galactose-binding protein. Thiodigalactoside (TDG) presents a scaffold for construction of galectin inhibitors, and its inhibition of galectin- 1 has already demonstrated beneficial effects as an adjuvant with vaccine immunotherapy, thereby improving the survival outcome of tumour-challenged mice. A novel approach-replacing galactose with its C2 epimer, talose-offers an alternative framework, as extensions at C2 permit exploitation of a galectin- 3-specific binding groove, thereby facilitating the design of selective inhibitors. We report the synthesis of thioditaloside (TDT) and crystal structures of the galectin-3 carbohydrate recognition domain in complexes with TDT and TDG. The different abilities of galactose and talose to anchor to the protein correlate with molecular dynamics studies, likely explaining the relative disaccharide binding affinities. The feasibility of a TDT scaffold to enable access to a particular galectin-3 binding groove and the need for modifications to optimise such a scaffold for use in the design of potent and selective inhibitors are assessed.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.publisherWiley-VCH
dc.publisher.placeGermany
dc.relation.ispartofstudentpublicationY
dc.relation.ispartofpagefrom1331
dc.relation.ispartofpageto1342
dc.relation.ispartofissue11
dc.relation.ispartofjournalChemBioChem
dc.relation.ispartofvolume14
dc.rights.retentionY
dc.subject.fieldofresearchStructural Biology (incl. Macromolecular Modelling)
dc.subject.fieldofresearchBiologically Active Molecules
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchcode060112
dc.subject.fieldofresearchcode030401
dc.subject.fieldofresearchcode0304
dc.subject.fieldofresearchcode0601
dc.titleInvestigation into the Feasibility of Thioditaloside as a Novel Scaffold for Galectin-3-Specific Inhibitors
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.date.issued2013
gro.hasfulltextNo Full Text
gro.griffith.authorGrice, Darren D.
gro.griffith.authorWilson, Jenny C.
gro.griffith.authorPearson, Andrew G.
gro.griffith.authorCollins, Patrick
gro.griffith.authorBlanchard, Helen
gro.griffith.authorGagarinov, Ivan A.
gro.griffith.authorBum-Erdene, KB
gro.griffith.authorWinger, Moritz


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