Design of Poly-Catechol Biodynamers for Potentiation of Antibiotic Efficacy against Drug-Resistant Bacteria
Lena Zeroug-Metz, Kristela Shehu, Justine Bassil, Justin Podlecki, Philipp Sonntag, Marcus Koch, Anastasia Christoulaki, Eric Buhler, Anna K. H. Hirsch, Annette Kraegeloh, Marc Schneider, Sangeun Lee
TL;DR
This paper introduces a new water-soluble polymer that boosts antibiotic effectiveness against drug-resistant bacteria by generating reactive oxygen species.
Contribution
A novel biodynamer with high catechol content and pH-responsive degradation is developed to enhance antibiotic efficacy.
Findings
DOPA-BD releases 3-fold more DOPA-hydrazide under acidic infection conditions.
The polymer synergistically enhances Azithromycin's efficacy 4-fold against resistant E. coli.
DOPA-BD remains stable for 72 hours in physiological buffer and induces ROS production in bacteria.
Abstract
Catechol-modified polymers, such as DOPA-functionalized systems, have recently gained significant interest for a variety of biomedical applications, particularly in their role as antibacterial adjuvants due to their oxidative activity and ability to generate reactive oxygen species (ROS). Current catechol-functionalized polymers, however, often suffer from a restricted number of catechol groups, limited biocompatibility and solubility, and low stability due to the rapid oxidation under physiological conditions. In this study, we developed a water-soluble, biocompatible DOPA-modified biodynamer (DOPA-BD), leveraging the principles of constitutional dynamic chemistry (CDC). DOPA-BD was synthesized via polycondensation of DOPA-hydrazide and the hexaethylene glycol-conjugated carbazole dialdehyde (CA-HG), forming dynamic imine and acylhydrazone linkages between the monomers. As a result of…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Figure 25
Figure 26
Figure 27
Figure 28
Figure 29
Figure 30
Figure 31
Figure 32Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsAntimicrobial agents and applications · Biopolymer Synthesis and Applications · Orthopedic Infections and Treatments