ArticleThe Journal of antibiotics2017
Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of β-lactams.
Article in The Journal of antibiotics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- The Oligosaccharyltransferase Catalytic Subunit PsSTT3B Is Required for Asexual Development and Pathogenicity inJournal of fungi (Basel, Switzerland) · 2026Article
- Post-translational modifications of GlmR integrate metabolic and stress signals to maintain cell envelope homeostasis in Bacillus subtilis.PLoS genetics · 2026Article
- Evaluation of the cytotoxicity and antibacterial activity of a synthetic tunicamycin derivative againstFrontiers in microbiology · 2025Article
- TunR2, a novel mode-of-action tunicamycin-type antibiotic: Pharmacokinetics in C57BL/6 mouse and Holstein cattle.PloS one · 2025Article
- Glycosylation of canine tetherin is essential for its antiviral activity against H3N2 canine influenza virus.Frontiers in veterinary science · 2025Article
- Tunicamycins from Marine-DerivedMarine drugs · 2024Article
- The tunicamycin derivative TunR2 exhibits potent antibiotic properties with low toxicity in an in vivo Mycobacterium marinum-zebrafish TB infection model.The Journal of antibiotics · 2024Article
- Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in the Therapeutic Implication of Cancers.Cells · 2024Review
- Heterologous Expression and Bioactivity Determination ofInternational journal of molecular sciences · 2023Article
- Ouabain-Induced Changes in the Expression of Voltage-Gated Potassium Channels in Epithelial Cells Depend on Cell-Cell Contacts.International journal of molecular sciences · 2022Article
- Concise Synthesis of Tunicamycin V and Discovery of a Cytostatic DPAGT1 Inhibitor.Angewandte Chemie (International ed. in English) · 2022Article
- Tunicamycin Protects against LPS-Induced Lung Injury.Pharmaceuticals (Basel, Switzerland) · 2022Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors.Journal of medicinal chemistry · 2020Article
- Synergistic enhancement of beta-lactam antibiotics by modified tunicamycin analogs TunR1 and TunR2.The Journal of antibiotics · 2019Article
- Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.Cell · 2018Article
- Selective catalytic hydrogenation of the N-acyl and uridyl double bonds in the tunicamycin family of protein N-glycosylation inhibitors.The Journal of antibiotics · 2017Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tunicamycins (TUN) are inhibitors of the UDP-HexNAc: polyprenol-P HexNAc-1-P transferase family of enzymes, which initiate the biosynthesis of bacterial peptidoglycan and catalyze the first step in eukaryotic protein N-glycosylation. The TUN are therefore general and potent toxins to both eukaryotes and prokaryotes. Screening a library of synthetic TUN against Bacillus and yeast identified TUN that are antibacterial, but have significantly reduced eukaryotic toxicity. One of these (Tun-15:0) differs from the native TUN control only by the lack of the conjugated double bond in the tunicaminyl N-acyl group. Tun-15:0 also showed reduced inhibition for protein N-glycosylation in a Pichia-based bioassay. Natural TUN was subsequently modified by chemically reducing the N-acyl double bond (TunR1) or both the N-acyl and uridyl double bonds (TunR2). TunR1 and TunR2 retain their antibacterial activity, but with considerably reduced eukaryotic toxicity. In protein N-glycosylation bioassays, TunR1 is a less potent inhibitor than native TUN and TunR2 is entirely inactive. Importantly, the less toxic TunR1 and TunR2 both enhance the antibacterial activity of β-lactams: oxacillin by 32- to 64-fold, comparable with native TUN, and with similar enhancements for methicillin and penicillin G. Hence, the modified TUNs, TunR1 and TunR2, are potentially important as less-toxic synergistic enhancers of the β-lactams.
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