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dc.contributor.authorHartman, Alwin M
dc.contributor.authorJumde, Varsha R
dc.contributor.authorElgaher, Walid A M
dc.contributor.authorTe Poele, Evelien M
dc.contributor.authorDijkhuizen, Lubbert
dc.contributor.authorHirsch, Anna K H
dc.date.accessioned2020-08-03T13:41:25Z
dc.date.available2020-08-03T13:41:25Z
dc.date.issued2020-06-16
dc.identifier.citationChemMedChem. 2020;10.1002/cmdc.202000222. doi:10.1002/cmdc.202000222.en_US
dc.identifier.pmid32542998
dc.identifier.doi10.1002/cmdc.202000222
dc.identifier.urihttp://hdl.handle.net/10033/622378
dc.description.abstractWe applied dynamic combinatorial chemistry (DCC) to find novel ligands of the bacterial virulence factor glucosyltransferase (GTF) 180. GTFs are the major producers of extracellular polysaccharides, which are important factors in the initiation and development of cariogenic dental biofilms. Following a structure-based strategy, we designed a series of 36 glucose- and maltose-based acylhydrazones as substrate mimics. Synthesis of the required mono- and disaccharide-based aldehydes set the stage for DCC experiments. Analysis of the dynamic combinatorial libraries (DCLs) by UPLC-MS revealed major amplification of four compounds in the presence of GTF180. Moreover, we found that derivatives of the glucose-acceptor maltose at the C1-hydroxy group act as glucose-donors and are cleaved by GTF180. The synthesized hits display medium to low binding affinity (KD values of 0.4-10.0 mm) according to surface plasmon resonance. In addition, they were investigated for inhibitory activity in GTF-activity assays. The early-stage DCC study reveals that careful design of DCLs opens up easy access to a broad class of novel compounds that can be developed further as potential inhibitors.en_US
dc.language.isoenen_US
dc.publisherWiley-VCHen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectdrug discoveryen_US
dc.subjectdynamic combinatorial chemistryen_US
dc.subjectglucosyltransferaseen_US
dc.subjectglycosidesen_US
dc.subjectsynthesisen_US
dc.titlePotential Dental Biofilm Inhibitors: Dynamic Combinatorial Chemistry Affords Sugar-Based Molecules that Target Bacterial Glucosyltransferase.en_US
dc.typeArticleen_US
dc.identifier.eissn1860-7187
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalChemMedChemen_US
refterms.dateFOA2020-08-03T13:41:26Z
dc.source.journaltitleChemMedChem
dc.source.countryInternational
dc.source.countryGermany


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