Source:http://linkedlifedata.com/resource/pubmed/id/18721837
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2008-10-22
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pubmed:abstractText |
The proline-rich antimicrobial peptide dimer, A3-APO, was designed based on a statistical analysis of native antibacterial peptide and protein sequences. Analysis of a series of structural analogs failed to identify any single or multiple amino acid modification or architectural changes that would significantly improve its potential as a clinical therapeutic. However, a single chain Chex1-Arg20 version, a natural in vivo metabolite, showed a 2 to 8-fold increase in activity against test Enterobacteriaceae strains. In addition to bacterial species close to Escherichia coli in phylogeny, A3-APO analogs were able to effectively kill Pseudomonas aeruginosa and Staphylococcus saprophyticus. Antibacterial efficacy analysis together with biochemical experiments provided further evidence for a multiple mode of action of A3-APO that includes binding and inhibition of the bacterial heat shock protein DnaK. Through inactivating of resistance enzymes, A3-APO was able to recover the lost activity of conventional antibiotics including chloramphenicol, beta-lactams, sulfonamides or trimethoprim against multidrug resistant strains with partial or full synergy. However, the synergy appeared to be individual strain and small molecule drug combination-dependent.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Escherichia coli Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase,
http://linkedlifedata.com/resource/pubmed/chemical/dnaK protein, E coli
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0196-9781
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1878-86
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pubmed:meshHeading |
pubmed-meshheading:18721837-Amino Acid Sequence,
pubmed-meshheading:18721837-Anti-Bacterial Agents,
pubmed-meshheading:18721837-Drug Design,
pubmed-meshheading:18721837-Drug Synergism,
pubmed-meshheading:18721837-Escherichia coli Proteins,
pubmed-meshheading:18721837-HSP70 Heat-Shock Proteins,
pubmed-meshheading:18721837-Klebsiella pneumoniae,
pubmed-meshheading:18721837-Microbial Sensitivity Tests,
pubmed-meshheading:18721837-Molecular Sequence Data,
pubmed-meshheading:18721837-Peptides,
pubmed-meshheading:18721837-Proline,
pubmed-meshheading:18721837-Protein Binding,
pubmed-meshheading:18721837-Structure-Activity Relationship,
pubmed-meshheading:18721837-beta-Galactosidase
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pubmed:year |
2008
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pubmed:articleTitle |
Scope and limitations of the designer proline-rich antibacterial peptide dimer, A3-APO, alone or in synergy with conventional antibiotics.
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pubmed:affiliation |
Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, United States.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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