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doi:10.22028/D291-39078
Titel: | Potential Dental Biofilm Inhibitors: Dynamic Combinatorial Chemistry Affords Sugar-Based Molecules that Target Bacterial Glucosyltransferase |
VerfasserIn: | Hartman, Alwin M. Jumde, Varsha R. Elgaher, Walid A. M. Te Poele, Evelien M. Dijkhuizen, Lubbert Hirsch, Anna K. H. |
Sprache: | Englisch |
Titel: | ChemMedChem |
Bandnummer: | 16 (2021) |
Heft: | 1 |
Seiten: | 113-123 |
Verlag/Plattform: | Wiley |
Erscheinungsjahr: | 2020 |
Freie Schlagwörter: | drug discovery dynamic combinatorial chemistry glucosyltransferase glycosides synthesis |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | We 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. |
DOI der Erstveröffentlichung: | 10.1002/cmdc.202000222 |
URL der Erstveröffentlichung: | https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cmdc.202000222 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-390783 hdl:20.500.11880/35238 http://dx.doi.org/10.22028/D291-39078 |
ISSN: | 1860-7187 1860-7179 |
Datum des Eintrags: | 16-Feb-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://chemistry-europe.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fcmdc.202000222&file=cmdc202000222-sup-0001-misc_information.pdf |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Pharmazie |
Professur: | NT - Prof. Dr. Anna Hirsch |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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ChemMedChem - 2020 - Hartman - Potential Dental Biofilm Inhibitors Dynamic Combinatorial Chemistry Affords Sugar‐Based.pdf | 2,87 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons