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dc.contributor.authorBohari, Mohammad H
dc.contributor.authorYu, Xing
dc.contributor.authorKishor, Chandan
dc.contributor.authorPatel, Brijesh
dc.contributor.authorGo, Rob Marc
dc.contributor.authorSeyedi, Hadieh A Eslampanah
dc.contributor.authorVinik, Yaron
dc.contributor.authorGrice, I Darren
dc.contributor.authorZick, Yehiel
dc.contributor.authorBlanchard, Helen
dc.date.accessioned2019-07-04T12:39:56Z
dc.date.available2019-07-04T12:39:56Z
dc.date.issued2018
dc.identifier.issn1860-7179
dc.identifier.doi10.1002/cmdc.201800224
dc.identifier.urihttp://hdl.handle.net/10072/382132
dc.description.abstractGalectin‐8 is a β‐galactoside‐recognising protein that has a role in the regulation of bone remodelling and is an emerging new target for tackling diseases with associated bone loss. We have designed and synthesised methyl 3‐O‐[1‐carboxyethyl]‐β‐d‐galactopyranoside (compound 6) as a ligand to target the N‐terminal domain of galectin‐8 (galectin‐8N). Our design involved molecular dynamics (MD) simulations that predicted 6 to mimic the interactions made by the galactose ring as well as the carboxylic acid group of 3′‐O‐sialylated lactose (3′‐SiaLac), with galectin‐8N. Isothermal titration calorimetry (ITC) determined that the binding affinity of galectin‐8N for 6 was 32.8 μm, whereas no significant affinity was detected for the C‐terminal domain of galectin‐8 (galectin‐8C). The crystal structure of the galectin‐8N–6 complex validated the predicted binding conformation and revealed the exact protein–ligand interactions that involve evolutionarily conserved amino acids of galectin and also those unique to galectin‐8N for recognition. Overall, we have initiated and demonstrated a rational ligand design campaign to develop a monosaccharide‐based scaffold as a binder of galectin‐8.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWiley
dc.publisher.placeGermany
dc.relation.ispartofpagefrom1664
dc.relation.ispartofpageto1672
dc.relation.ispartofissue16
dc.relation.ispartofjournalChemMedChem
dc.relation.ispartofvolume13
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchMedicinal and biomolecular chemistry not elsewhere classified
dc.subject.fieldofresearchOrganic chemistry
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode340499
dc.subject.fieldofresearchcode3405
dc.subject.fieldofresearchcode3214
dc.titleStructure-Based Design of a Monosaccharide Ligand Targeting Galectin-8
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.hasfulltextNo Full Text
gro.griffith.authorGrice, Darren D.
gro.griffith.authorBlanchard, Helen
gro.griffith.authorYu, Xing
gro.griffith.authorPatel, Brijesh A.
gro.griffith.authorBohari, Mohammad
gro.griffith.authorKishor, Chandan
gro.griffith.authorEslampanah Seyedi, Hadieh A.
gro.griffith.authorGo, Rob


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