ArticleMolecular diversity2011
Potent antimicrobial small molecules screened as inhibitors of tyrosine recombinases and Holliday junction-resolving enzymes.
Article in Molecular diversity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Recent progress in probing small molecule interactions with DNA.Biophysical reviews · 2025Review
- Synthesis of Diazacyclic and Triazacyclic Small-Molecule Libraries Using Vicinal Chiral Diamines Generated from Modified Short Peptides and Their Application for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Polyheterocyclic peptidomimetics: Parallel solid phase synthesis of oligo cyclic guanidines and their inhibition activity against Mycobacterium tuberculosis DNA gyrase.Bioorganic & medicinal chemistry letters · 2023Article
- Interactions of small molecules with DNA junctions.Nucleic acids research · 2022Review
- Discovery of Nanomolar Melanocortin-3 Receptor (MC3R)-Selective Small Molecule Pyrrolidine Bis-Cyclic Guanidine Agonist Compounds Via a High-Throughput "Unbiased" Screening Campaign.Journal of medicinal chemistry · 2021Article
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- Identification of Bis-Cyclic Guanidines as Antiplasmodial Compounds from Positional Scanning Mixture-Based Libraries.Molecules (Basel, Switzerland) · 2019Article
- Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] using mixture-based combinatorial libraries.International journal of antimicrobial agents · 2018Article
- Identification of a Hit Series of Antileishmanial Compounds through the Use of Mixture-Based Libraries.ACS medicinal chemistry letters · 2017Article
- Small-Molecule Inhibitors Targeting Topoisomerase I as Novel Antituberculosis Agents.Antimicrobial agents and chemotherapy · 2016Article
- Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.Journal of medicinal chemistry · 2015Article
- Novel pyrrolidine diketopiperazines selectively inhibit melanoma cells via induction of late-onset apoptosis.Journal of medicinal chemistry · 2014Article
- Scaffold ranking and positional scanning utilized in the discovery of nAChR-selective compounds suitable for optimization studies.Journal of medicinal chemistry · 2013Article
- Synthesis of cyclic guanidines via Pd-catalyzed alkene carboamination.Organic letters · 2013Article
- The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.Molecules (Basel, Switzerland) · 2013Article
- wrwyrggrywrw is a single-chain functional analog of the Holliday junction-binding homodimer, (wrwycr)2.Peptides · 2013Article
- HTS by NMR of combinatorial libraries: a fragment-based approach to ligand discovery.Chemistry & biology · 2013Article
- Tumor cell death mediated by peptides that recognize branched intermediates of DNA replication and repair.PloS one · 2013Article
- Similarities between exogenously- and endogenously-induced envelope stress: the effects of a new antibacterial molecule, TPI1609-10.PloS one · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Holliday junctions (HJs) are critical intermediates in many recombination-dependent DNA repair pathways. Our lab has previously identified several hexameric peptides that target HJ intermediates formed in DNA recombination reactions. One of the most potent peptides, WRWYCR, is active as a homodimer and has shown bactericidal activity partly because of its ability to interfere with DNA repair proteins that act upon HJs. To increase the possibility of developing a therapeutic targeting DNA repair, we searched for small molecule inhibitors that were functional surrogates of the peptides. Initial screens of heterocyclic small molecule libraries resulted in the identification of several N-methyl aminocyclic thiourea inhibitors. Like the peptides, these inhibitors trapped HJs formed during recombination reactions in vitro, but were less potent than the peptides in biochemical assays and had little antibacterial activity. In this study, we describe the screening of a second set of libraries containing somewhat larger and more symmetrical scaffolds in an effort to mimic the symmetry of a WRWYCR homodimer and its target. From this screen, we identified several pyrrolidine bis-cyclic guanidine inhibitors that also interfere with processing of HJs in vitro and are potent inhibitors of Gram-negative and especially Gram-positive bacterial growth. These molecules are proof-of-principle of a class of compounds with novel activities, which may in the future be developed into a new class of antibiotics that will expand the available choices for therapy against drug-resistant bacteria.
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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.