D-enantiomers of 15-residue cecropin A-melittin hybrids.
Identifieur interne : 002A06 ( Ncbi/Merge ); précédent : 002A05; suivant : 002A07D-enantiomers of 15-residue cecropin A-melittin hybrids.
Auteurs : E L Merrifield [États-Unis] ; S A Mitchell ; J. Ubach ; H G Boman ; D. Andreu ; R B MerrifieldSource :
- International journal of peptide and protein research [ 0367-8377 ]
Descripteurs français
- KwdFr :
- Antibactériens (), Bactéries à Gram négatif (), Bactéries à Gram positif (), Conductivité électrique, Conformation des protéines, Dichroïsme circulaire, Fragments peptidiques (), Hormones des insectes (), Multimérisation de protéines, Mélittine (), Peptides (), Peptides antimicrobiens cationiques, Spectrophotométrie, Stabilité de médicament, Stéréoisomérie, Trypsine.
- MESH :
- Antibactériens, Bactéries à Gram négatif, Bactéries à Gram positif, Conductivité électrique, Conformation des protéines, Dichroïsme circulaire, Fragments peptidiques, Hormones des insectes, Multimérisation de protéines, Mélittine, Peptides, Peptides antimicrobiens cationiques, Spectrophotométrie, Stabilité de médicament, Stéréoisomérie, Trypsine.
English descriptors
- KwdEn :
- Anti-Bacterial Agents (chemistry), Antimicrobial Cationic Peptides, Circular Dichroism, Drug Stability, Electric Conductivity, Gram-Negative Bacteria (drug effects), Gram-Positive Bacteria (drug effects), Insect Hormones (chemistry), Melitten (chemistry), Peptide Fragments (chemistry), Peptides (chemistry), Protein Conformation, Protein Multimerization, Spectrophotometry, Stereoisomerism, Trypsin.
- MESH :
- chemical , chemistry : Anti-Bacterial Agents, Insect Hormones, Melitten, Peptide Fragments, Peptides.
- chemical : Antimicrobial Cationic Peptides, Trypsin.
- drug effects : Gram-Negative Bacteria, Gram-Positive Bacteria.
- Circular Dichroism, Drug Stability, Electric Conductivity, Protein Conformation, Protein Multimerization, Spectrophotometry, Stereoisomerism.
Abstract
The all-D enantiomers of six 15-residue hybrids of cecropin A and melittin were synthesized. They contained the seven N-terminal residues of cecropin A, followed by eight residues from the N-terminal region of melittin. They were pure and of the correct composition and structure. The peptides were compared with their all-L enantiomers. The L and D isomer pairs were each exact mirror images by circular dichroism at several concentrations of hexafluoroisopropanol, and at 12 or 20% were highly helical. The L analogs were rapidly hydrolyzed by trypsin but the D analogs were very resistant, making them suitable candidates for orally active drugs. These 15-mers did not form ion channels in normal lipid bilayers made in decane, but those bilayers made in squalene were thinner and the peptides did form ion-conducting channels. The D/L pairs of peptides were very active antibiotics against five representative Gram-negative and Gram-positive bacteria. In each case the D and L isomers were essentially equally active within experimental error. This is interpreted to mean that the peptides do not act by tight interactions with chiral receptors, enzymes or lipids. The action of these peptides against these organisms is best explained by self-aggregation and the formation of ion-conducting pores across bacterial membranes.
DOI: 10.1111/j.1399-3011.1995.tb00592.x
PubMed: 8537174
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002807
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- to stream PubMed, to step Checkpoint: 002B10
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pubmed:8537174Le document en format XML
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<author><name sortKey="Ubach, J" sort="Ubach, J" uniqKey="Ubach J" first="J" last="Ubach">J. Ubach</name>
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<author><name sortKey="Boman, H G" sort="Boman, H G" uniqKey="Boman H" first="H G" last="Boman">H G Boman</name>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anti-Bacterial Agents (chemistry)</term>
<term>Antimicrobial Cationic Peptides</term>
<term>Circular Dichroism</term>
<term>Drug Stability</term>
<term>Electric Conductivity</term>
<term>Gram-Negative Bacteria (drug effects)</term>
<term>Gram-Positive Bacteria (drug effects)</term>
<term>Insect Hormones (chemistry)</term>
<term>Melitten (chemistry)</term>
<term>Peptide Fragments (chemistry)</term>
<term>Peptides (chemistry)</term>
<term>Protein Conformation</term>
<term>Protein Multimerization</term>
<term>Spectrophotometry</term>
<term>Stereoisomerism</term>
<term>Trypsin</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Antibactériens ()</term>
<term>Bactéries à Gram négatif ()</term>
<term>Bactéries à Gram positif ()</term>
<term>Conductivité électrique</term>
<term>Conformation des protéines</term>
<term>Dichroïsme circulaire</term>
<term>Fragments peptidiques ()</term>
<term>Hormones des insectes ()</term>
<term>Multimérisation de protéines</term>
<term>Mélittine ()</term>
<term>Peptides ()</term>
<term>Peptides antimicrobiens cationiques</term>
<term>Spectrophotométrie</term>
<term>Stabilité de médicament</term>
<term>Stéréoisomérie</term>
<term>Trypsine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anti-Bacterial Agents</term>
<term>Insect Hormones</term>
<term>Melitten</term>
<term>Peptide Fragments</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antimicrobial Cationic Peptides</term>
<term>Trypsin</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gram-Negative Bacteria</term>
<term>Gram-Positive Bacteria</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Circular Dichroism</term>
<term>Drug Stability</term>
<term>Electric Conductivity</term>
<term>Protein Conformation</term>
<term>Protein Multimerization</term>
<term>Spectrophotometry</term>
<term>Stereoisomerism</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Antibactériens</term>
<term>Bactéries à Gram négatif</term>
<term>Bactéries à Gram positif</term>
<term>Conductivité électrique</term>
<term>Conformation des protéines</term>
<term>Dichroïsme circulaire</term>
<term>Fragments peptidiques</term>
<term>Hormones des insectes</term>
<term>Multimérisation de protéines</term>
<term>Mélittine</term>
<term>Peptides</term>
<term>Peptides antimicrobiens cationiques</term>
<term>Spectrophotométrie</term>
<term>Stabilité de médicament</term>
<term>Stéréoisomérie</term>
<term>Trypsine</term>
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<front><div type="abstract" xml:lang="en">The all-D enantiomers of six 15-residue hybrids of cecropin A and melittin were synthesized. They contained the seven N-terminal residues of cecropin A, followed by eight residues from the N-terminal region of melittin. They were pure and of the correct composition and structure. The peptides were compared with their all-L enantiomers. The L and D isomer pairs were each exact mirror images by circular dichroism at several concentrations of hexafluoroisopropanol, and at 12 or 20% were highly helical. The L analogs were rapidly hydrolyzed by trypsin but the D analogs were very resistant, making them suitable candidates for orally active drugs. These 15-mers did not form ion channels in normal lipid bilayers made in decane, but those bilayers made in squalene were thinner and the peptides did form ion-conducting channels. The D/L pairs of peptides were very active antibiotics against five representative Gram-negative and Gram-positive bacteria. In each case the D and L isomers were essentially equally active within experimental error. This is interpreted to mean that the peptides do not act by tight interactions with chiral receptors, enzymes or lipids. The action of these peptides against these organisms is best explained by self-aggregation and the formation of ion-conducting pores across bacterial membranes.</div>
</front>
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<Title>International journal of peptide and protein research</Title>
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<ArticleTitle>D-enantiomers of 15-residue cecropin A-melittin hybrids.</ArticleTitle>
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<Abstract><AbstractText>The all-D enantiomers of six 15-residue hybrids of cecropin A and melittin were synthesized. They contained the seven N-terminal residues of cecropin A, followed by eight residues from the N-terminal region of melittin. They were pure and of the correct composition and structure. The peptides were compared with their all-L enantiomers. The L and D isomer pairs were each exact mirror images by circular dichroism at several concentrations of hexafluoroisopropanol, and at 12 or 20% were highly helical. The L analogs were rapidly hydrolyzed by trypsin but the D analogs were very resistant, making them suitable candidates for orally active drugs. These 15-mers did not form ion channels in normal lipid bilayers made in decane, but those bilayers made in squalene were thinner and the peptides did form ion-conducting channels. The D/L pairs of peptides were very active antibiotics against five representative Gram-negative and Gram-positive bacteria. In each case the D and L isomers were essentially equally active within experimental error. This is interpreted to mean that the peptides do not act by tight interactions with chiral receptors, enzymes or lipids. The action of these peptides against these organisms is best explained by self-aggregation and the formation of ion-conducting pores across bacterial membranes.</AbstractText>
</Abstract>
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<MeshHeading><DescriptorName UI="D011487" MajorTopicYN="N">Protein Conformation</DescriptorName>
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<MeshHeading><DescriptorName UI="D055503" MajorTopicYN="N">Protein Multimerization</DescriptorName>
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<MeshHeading><DescriptorName UI="D013053" MajorTopicYN="N">Spectrophotometry</DescriptorName>
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<name sortKey="Merrifield, R B" sort="Merrifield, R B" uniqKey="Merrifield R" first="R B" last="Merrifield">R B Merrifield</name>
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