ArticleJournal of the American Chemical Society2015
Total syntheses and initial evaluation of [Ψ[C(═S)NH]Tpg⁴]vancomycin, [Ψ[C(═NH)NH]Tpg⁴]vancomycin, [Ψ[CH₂NH]Tpg⁴]vancomycin, and their (4-chlorobiphenyl)methyl derivatives: synergistic binding pocket and peripheral modifications for the glycopeptide antibiotics.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 68 citations in OpenAlex.
- Review
- Tetrachloromaxamycins: Divergent Total Synthesis and Initial Assessments.The Journal of organic chemistry · 2024Article
- Vancomycin-resistant Staphylococcus aureus (VRSA) can overcome the cost of antibiotic resistance and may threaten vancomycin's clinical durability.PLoS pathogens · 2024Article
- Thioimidates provide general access to thioamide, amidine, and imidazolone peptide-bond isosteres.Methods in enzymology · 2024Article
- Tetrachlorovancomycin: Total Synthesis of a Designed Glycopeptide Antibiotic of Reduced Synthetic Complexity.Journal of the American Chemical Society · 2023Article
- Divergent Total Synthesis and Characterization of Maxamycins.Journal of the American Chemical Society · 2023Article
- Article
- Maxamycins: Durable Antibiotics Derived by Rational Redesign of Vancomycin.Accounts of chemical research · 2020Article
- The quest for supernatural products: the impact of total synthesis in complex natural products medicinal chemistry.Natural product reports · 2020Review
- Next-Generation Total Synthesis of Vancomycin.Journal of the American Chemical Society · 2020Article
- Vancomycin C-Terminus Guanidine Modifications and Further Insights into an Added Mechanism of Action Imparted by a Peripheral Structural Modification.ACS infectious diseases · 2020Article
- Treating a Global Health Crisis with a Dose of Synthetic Chemistry.ACS central science · 2020Article
- Instructive Advances in Chemical Microbiology Inspired by Nature's Diverse Inventory of Molecules.ACS infectious diseases · 2020Review
- C1-CBP-vancomycin: Impact of a Vancomycin C-Terminus Trimethylammonium Cation on Pharmacological Properties and Insights into Its Newly Introduced Mechanism of Action.The Journal of organic chemistry · 2020Article
- Structure-Activity Relationship of Peptide-Conjugated Chloramphenicol for InhibitingJournal of medicinal chemistry · 2019Article
- Recent Progress in Natural-Product-Inspired Programs Aimed To Address Antibiotic Resistance and Tolerance.Journal of medicinal chemistry · 2019Review
- Exploration of the site-specific nature and generalizability of a trimethylammonium salt modification on vancomycin: A-ring derivatives.Tetrahedron · 2019Article
- Biosynthesis and Chemical Applications of Thioamides.ACS chemical biology · 2019Review
- The race for antimicrobials in the multidrug resistance era.Microbial biotechnology · 2018Article
- N-Terminus Alkylation of Vancomycin: Ligand Binding Affinity, Antimicrobial Activity, and Site-Specific Nature of Quaternary Trimethylammonium Salt Modification.ACS infectious diseases · 2018Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Full details of studies are disclosed on the total syntheses of binding pocket analogues of vancomycin bearing the peripheral L-vancosaminyl-1,2-D-glucosyl disaccharide that contain changes to a key single atom in the residue-4 amide (residue-4 carbonyl O → S, NH, H2) designed to directly address the underlying molecular basis of resistance to vancomycin. Also disclosed are studies piloting the late-stage transformations conducted on the synthetically more accessible C-terminus hydroxymethyl aglycon derivatives and full details of the peripheral chlorobiphenyl functionalization of all of the binding-pocket-modified vancomycin analogues designed for dual D-Ala-D-Ala/D-Ala-D-Lac binding. Their collective assessment indicates that combined binding pocket and chlorobiphenyl peripherally modified analogues exhibit a remarkable spectrum of antimicrobial activity (VSSA, MRSA, and VanA and VanB VRE) and impressive potencies against both vancomycin-sensitive and vancomycin-resistant bacteria (MICs = 0.06-0.005 and 0.5-0.06 μg/mL for the amidine and methylene analogues, respectively) and likely benefit from two independent and synergistic mechanisms of action, only one of which is dependent on D-Ala-D-Ala/D-Ala-D-Lac binding. Such analogues are likely to display especially durable antibiotic activity that is not prone to rapidly acquired clinical resistance.
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