Potential Dental Biofilm Inhibitors: Dynamic Combinatorial Chemistry Affords Sugar-Based Molecules that Target Bacterial Glucosyltransferase.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsHartman, Alwin M
Jumde, Varsha R
Elgaher, Walid A M
Te Poele, Evelien M
Hirsch, Anna K H
MetadataShow full item record
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.
CitationChemMedChem. 2020;10.1002/cmdc.202000222. doi:10.1002/cmdc.202000222.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Molecule Targeting Glucosyltransferase Inhibits Streptococcus mutans Biofilm Formation and Virulence.
- Authors: Ren Z, Cui T, Zeng J, Chen L, Zhang W, Xu X, Cheng L, Li M, Li J, Zhou X, Li Y
- Issue date: 2016 Jan
- Structure-Based Discovery of Small Molecule Inhibitors of Cariogenic Virulence.
- Authors: Zhang Q, Nijampatnam B, Hua Z, Nguyen T, Zou J, Cai X, Michalek SM, Velu SE, Wu H
- Issue date: 2017 Jul 20
- Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target.
- Authors: Frei P, Pang L, Silbermann M, Eriş D, Mühlethaler T, Schwardt O, Ernst B
- Issue date: 2017 Aug 25
- Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents.
- Authors: Nijampatnam B, Casals L, Zheng R, Wu H, Velu SE
- Issue date: 2016 Aug 1
- DNA-Encoded Dynamic Combinatorial Chemical Libraries.
- Authors: Reddavide FV, Lin W, Lehnert S, Zhang Y
- Issue date: 2015 Jun 26