ArticleProceedings of the National Academy of Sciences of the United States of America2017
Peripheral modifications of [Ψ[CH
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 198 citations in OpenAlex.
- Aza-Michael Quaternization: Addition of Tertiary Amines to Allenic Michael Acceptors Furnishes Quaternary Ammonium Compounds.JACS Au · 2026Article
- Guanidiniocarbonyl-Pyrrole (GCP) C- and N-Terminus Modifications of Vancomycin.The Journal of organic chemistry · 2025Article
- Photocatalytic generation of amidine carbon radicals for aminodihydroquinoline synthesis.Nature communications · 2025Article
- Supernatural Products.The Chemist · 2025Article
- Saarvienin A-A Novel Glycopeptide with Potent Activity against Drug-Resistant Bacteria.Angewandte Chemie (International ed. in English) · 2025Article
- The power of DNA-encoded chemical libraries in the battle against drug-resistant bacteria.RSC advances · 2025Review
- Strategic re-engineering of antibiotics.Nature reviews bioengineering · 2025Article
- Vancomycin-Teixobactin Conjugates.Journal of the American Chemical Society · 2025Article
- Review
- Tetrachloromaxamycins: Divergent Total Synthesis and Initial Assessments.The Journal of organic chemistry · 2024Article
- Amidine containing compounds: Antimicrobial activity and its potential in combating antimicrobial resistance.Heliyon · 2024Review
- Biguanide-Vancomycin Conjugates are Effective Broad-Spectrum Antibiotics against Actively Growing and Biofilm-Associated Gram-Positive and Gram-Negative ESKAPE Pathogens and Mycobacteria.Journal of the American Chemical Society · 2024Article
- Advances in the Synthesis of Biologically Active Quaternary Ammonium Compounds.International journal of molecular sciences · 2024Review
- The allure of targets for novel drugs.RSC medicinal chemistry · 2024Review
- Vancomycin-Polyguanidino Dendrimer Conjugates Inhibit Growth of Antibiotic-Resistant Gram-Positive and Gram-Negative Bacteria and Eradicate Biofilm-AssociatedACS infectious diseases · 2024Article
- Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin.Communications biology · 2023Article
- Deriving Novel Quaternary Ammonium Compound Disinfectant Scaffolds from a Natural Product: Mechanistic Insights of the Quaternization of Ianthelliformisamine C.ChemMedChem · 2023Article
- Tetrachlorovancomycin: Total Synthesis of a Designed Glycopeptide Antibiotic of Reduced Synthetic Complexity.Journal of the American Chemical Society · 2023Article
- Engineered Vancomycin, with Increased Interactions with Peptidoglycan Stem Peptide, Conquers Non-tuberculosis Mycobacteria.Journal of medicinal chemistry · 2023Article
- Conjugation of Vancomycin with a Single Arginine Improves Efficacy against Mycobacteria by More Effective Peptidoglycan Targeting.Journal of medicinal chemistry · 2023Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Subsequent to binding pocket modifications designed to provide dual d-Ala-d-Ala/d-Ala-d-Lac binding that directly overcome the molecular basis of vancomycin resistance, peripheral structural changes have been explored to improve antimicrobial potency and provide additional synergistic mechanisms of action. A C-terminal peripheral modification, introducing a quaternary ammonium salt, is reported and was found to provide a binding pocket-modified vancomycin analog with a second mechanism of action that is independent of d-Ala-d-Ala/d-Ala-d-Lac binding. This modification, which induces cell wall permeability and is complementary to the glycopeptide inhibition of cell wall synthesis, was found to provide improvements in antimicrobial potency (200-fold) against vancomycin-resistant Enterococci (VRE). Furthermore, it is shown that this type of C-terminal modification may be combined with a second peripheral (4-chlorobiphenyl)methyl (CBP) addition to the vancomycin disaccharide to provide even more potent antimicrobial agents [VRE minimum inhibitory concentration (MIC) = 0.01-0.005 μg/mL] with activity that can be attributed to three independent and synergistic mechanisms of action, only one of which requires d-Ala-d-Ala/d-Ala-d-Lac binding. Finally, it is shown that such peripherally and binding pocket-modified vancomycin analogs display little propensity for acquired resistance by VRE and that their durability against such challenges as well as their antimicrobial potency follow now predictable trends (three > two > one mechanisms of action). Such antibiotics are expected to display durable antimicrobial activity not prone to rapidly acquired clinical resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.