Abstract
CRAMP-18 is an 18-residue functional region, corresponding to residues 16-33 of a mouse-derived antibiotic peptide CRAMP. To develop novel antibiotic peptides possessing strong antibiotic activity against bacterial, fungal and tumor cells without hemolytic activity, three analogs of CRAMP-18 were synthesized containing either Leu- or Lys-substitution. Leu-substitution ([L(1, 8)]-CRAMP-18) in the hydrophobic helix face of CRAMP-18 induced a dramatic increase in antibiotic activity without a significant increase in hemolytic activity. Lys-substitution ([K(2, 13)]-CRAMP-18 or [K(9, 16)]-CRAMP-18) in the hydrophilic helix face produced a smaller response. Therefore, [L(1, 8)]-CRAMP-18 may be an attractive candidate for developing novel peptide antibiotics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Antifungal Agents / chemical synthesis*
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Antifungal Agents / pharmacology
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Antimicrobial Cationic Peptides*
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Aspergillus fumigatus / drug effects
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Bacteria / drug effects
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Cathelicidins
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Circular Dichroism
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Erythrocytes / drug effects
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Hemolysis
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Humans
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Mice
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Molecular Sequence Data
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Peptides / chemical synthesis*
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Peptides / chemistry
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Peptides / genetics
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Peptides / pharmacology
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Proteins / chemistry*
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Proteins / genetics
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Tumor Cells, Cultured
Substances
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Anti-Bacterial Agents
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Antifungal Agents
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Antimicrobial Cationic Peptides
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Antineoplastic Agents
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Cathelicidins
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Peptides
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Proteins