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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



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons