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Structure-microbici...
Structure-microbicidal activity relationship of synthetic fragments derived from the antibacterial alpha-helix of human lactoferrin.
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- Håversen, Liliana, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden
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- Kondori, Nahid, 1967 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden
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- Baltzer, Lars (författare)
- Linköpings universitet,Institutionen för fysik, kemi och biologi,Tekniska högskolan
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- Hanson, Lars Åke, 1934 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology,Univ Gothenburg, Dept Clin Immunol, S-41346 Gothenburg, Sweden
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- Dolphin, Gunnar (författare)
- Linköpings universitet,Institutionen för fysik, kemi och biologi,Tekniska högskolan
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- Dunér, K (författare)
- Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden
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- Mattsby-Baltzer, Inger, 1949 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden
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(creator_code:org_t)
- 2010
- 2010
- Engelska.
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Ingår i: Antimicrobial agents and chemotherapy. - 1098-6596 .- 0066-4804. ; 54:1, s. 418-25
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- There is a need for new microbicidal agents with therapeutic potential due to antibiotic resistance in bacteria and fungi. In this study, the structure-microbicidal activity relationship of amino acid residues 14 to 31 (sequence 14-31) from the N-terminal end, corresponding to the antibacterial alpha-helix of human lactoferrin (LF), was investigated by downsizing, alanine scanning, and substitution of amino acids. Microbicidal analysis (99% killing) was performed by a microplate assay using Escherichia coli, Staphylococcus aureus, and Candida albicans as test organisms. Starting from the N-terminal end, downsizing of peptide sequence 14-31 showed that the peptide sequence 19-31 (KCFQWQRNMRKVR, HL9) was the optimal length for antimicrobial activity. Furthermore, HL9 bound to lipid A/lipopolysaccharide, as shown by neutralizing endotoxic activity in a Limulus assay. Alanine scanning of peptide sequence 20-31 showed that Cys20, Trp23, Arg28, Lys29, or Arg31 was important for expressing full killing activity, particularly against C. albicans. Substituting the neutral hydrophilic amino acids Gln24 and Asn26 for Lys and Ala (HLopt2), respectively, enhanced microbicidal activity significantly against all test organisms compared to the amino acids natural counterpart, also, in comparison with HL9, HLopt2 had more than 10-fold-stronger fungicidal activity. Furthermore, HLopt2 was less affected by metallic salts than HL9. The microbicidal activity of HLopt2 was slightly reduced only at pH 7.0, as tested in the pH range of 4.5 to 7.5. The results showed that the microbicidal activity of synthetic peptide sequences, based on the antimicrobial alpha-helix region of LF, can be significantly enhanced by optimizing the length and substitution of neutral amino acids at specific positions, thus suggesting a sequence lead with therapeutic potential.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- Amino Acid Sequence
- Amino Acids
- chemistry
- Anti-Bacterial Agents
- chemical synthesis
- chemistry
- pharmacology
- Candida albicans
- drug effects
- Escherichia coli
- drug effects
- Humans
- Hydrogen-Ion Concentration
- Kinetics
- Lactoferrin
- chemical synthesis
- chemistry
- pharmacology
- Limulus Test
- Lipopolysaccharides
- pharmacology
- Metals
- chemistry
- Microbial Sensitivity Tests
- Milk
- Human
- microbiology
- Molecular Mimicry
- Molecular Sequence Data
- Peptide Fragments
- chemical synthesis
- chemistry
- pharmacology
- Protein Conformation
- Sodium Chloride
- chemistry
- Staphylococcus aureus
- drug effects
- Structure-Activity Relationship
- TECHNOLOGY
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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