ArticleJournal of the American Chemical Society2017
Discovery of a Potent Inhibitor Class with High Selectivity toward Clostridial Collagenases.
Article in Journal of the American Chemical Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Comparative chemical and biological study of essential oils and n-hexane extracts of Thymus vulgaris and Thymus serpyllum (Lamiaceae).Scientific reports · 2026Article
- Targeting of interaction between BB0323-BB0238 informs new paradigms in Lyme disease therapeutics.PLoS pathogens · 2026Article
- A conserved strategy to attack collagen: The activator domain in bacterial collagenases unwinds triple-helical collagen.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Upcycling poly(succinates) with amines to N-substituted succinimides over succinimide anion-based ionic liquids.Nature communications · 2024Article
- Unlocking the Potential of Collagenases: Structures, Functions, and Emerging Therapeutic Horizons.Biodesign research · 2024Article
- A Benchmark Study of Protein-Fragment Complex Structure Calculations withInternational journal of molecular sciences · 2023Article
- Discovery of New Microbial Collagenase Inhibitors.Life (Basel, Switzerland) · 2022Article
- Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases.Journal of medicinal chemistry · 2022Article
- The Structures and Binding Modes of Small-Molecule Inhibitors ofAntibiotics (Basel, Switzerland) · 2022Review
- Structure-Based Design of α-Substituted Mercaptoacetamides as Inhibitors of the Virulence Factor LasB fromACS infectious diseases · 2022Article
- Inhibition of Collagenase Q1 ofAdvanced therapeutics · 2022Article
- Candidates for Repurposing as Anti-Virulence Agents Based on the Structural Profile Analysis of Microbial Collagenase Inhibitors.Pharmaceutics · 2021Article
- Article
- Screening Collagenase Activity in Bacterial Lysate for Directed Enzyme Applications.International journal of molecular sciences · 2021Article
- Phosphonate as a Stable Zinc-Binding Group for "Pathoblocker" Inhibitors of Clostridial Collagenase H (ColH).ChemMedChem · 2021Article
- Biochemical characterisation of a collagenase from Bacillus cereus strain Q1.Scientific reports · 2021Article
- Towards the sustainable discovery and development of new antibiotics.Nature reviews. Chemistry · 2021Review
- Article
- Concepts and Core Principles of Fragment-Based Drug Design.Molecules (Basel, Switzerland) · 2019Review
- Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections.Beilstein journal of organic chemistry · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secreted virulence factors like bacterial collagenases are conceptually attractive targets for fighting microbial infections. However, previous attempts to develop potent compounds against these metalloproteases failed to achieve selectivity against human matrix metalloproteinases (MMPs). Using a surface plasmon resonance-based screening complemented with enzyme inhibition assays, we discovered an N-aryl mercaptoacetamide-based inhibitor scaffold that showed sub-micromolar affinities toward collagenase H (ColH) from the human pathogen Clostridium histolyticum. Moreover, these inhibitors also efficiently blocked the homologous bacterial collagenases, ColG from C. histolyticum, ColT from C. tetani, and ColQ1 from the Bacillus cereus strain Q1, while showing negligible activity toward human MMPs-1, -2, -3, -7, -8, and -14. The most active compound displayed a more than 1000-fold selectivity over human MMPs. This selectivity can be rationalized by the crystal structure of ColH with this compound, revealing a distinct non-primed binding mode to the active site. The non-primed binding mode presented here paves the way for the development of selective broad-spectrum bacterial collagenase inhibitors with potential therapeutic application in humans.
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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.