ArticlePloS one2011
New noncovalent inhibitors of penicillin-binding proteins from penicillin-resistant bacteria.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 43 citations in OpenAlex.
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Unraveling the mechanism of ceftaroline-induced allosteric regulation in penicillin-binding protein 2a: insights for novel antibiotic development against methicillin-resistantAntimicrobial agents and chemotherapy · 2023Article
- Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance.International journal of molecular sciences · 2023Review
- Discovery of Pyrrolidine-2,3-diones as Novel Inhibitors ofAntibiotics (Basel, Switzerland) · 2021Article
- Synergistic antibacterial activity between penicillenols and antibiotics against methicillin-resistantRoyal Society open science · 2018Article
- Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Bacterial proteases: targets for diagnostics and therapy.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2014Review
- In silico study on Penicillin derivatives and Cephalosporins for upper respiratory tract bacterial pathogens.3 Biotech · 2014Article
- Crystal structures of bifunctional penicillin-binding protein 4 from Listeria monocytogenes.Antimicrobial agents and chemotherapy · 2013Article
- Inhibition of DD-peptidases by a specific trifluoroketone: crystal structure of a complex with the Actinomadura R39 DD-peptidase.Biochemistry · 2013Article
- Inhibition of WTA synthesis blocks the cooperative action of PBPs and sensitizes MRSA to β-lactams.ACS chemical biology · 2013Article
- Development of new drugs for an old target: the penicillin binding proteins.Molecules (Basel, Switzerland) · 2012Review
- 4-quinolones as noncovalent inhibitors of high molecular mass penicillin-binding proteins.ACS medicinal chemistry letters · 2012Article
- High-throughput screening for novel inhibitors of Neisseria gonorrhoeae penicillin-binding protein 2.PloS one · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPenicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs β-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for β-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs. METHODOLOGY/PRINCIPAL
findingsOur in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains.
conclusionsWe found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria.
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