AI Article Synopsis
- Multidrug-resistant bacteria pose a major challenge in healthcare, especially with increased glycopeptide resistance reducing vancomycin’s effectiveness as a last-resort treatment.
- Researchers developed new compounds by attaching polycationic peptides to vancomycin, creating versions with up to 1000 times stronger antimicrobial activity that can effectively combat significant vancomycin resistance.
- The top candidate, FU002, showed promising results in treating bacterial infections in animal studies, indicating improved drug distribution and action within the body.
Article Abstract
Multidrug-resistant bacteria represent one of the biggest challenges facing modern medicine. The increasing prevalence of glycopeptide resistance compromises the efficacy of vancomycin, for a long time considered as the last resort for the treatment of resistant bacteria. To reestablish its activity, polycationic peptides were conjugated to vancomycin. By site-specific conjugation, derivatives that bear the peptide moiety at four different sites of the antibiotic were synthesized. The most potent compounds exhibited an approximately 1000-fold increased antimicrobial activity and were able to overcome the most important types of vancomycin resistance. Additional blocking experiments using d-Ala-d-Ala revealed a mode of action beyond inhibition of cell-wall formation. The antimicrobial potential of the lead candidate FU002 for bacterial infection treatments could be demonstrated in an in vivo study. Molecular imaging and biodistribution studies revealed that conjugation engenders superior pharmacokinetics.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323874 | PMC |
| http://dx.doi.org/10.1002/anie.202002727 | DOI Listing |
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