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Antimicrobial activity of rabbit CAP18-derived peptides
J W Larrick1, M Hirata, Y Shimomoura
1Palo Alto Institute of Molecular Medicine, Mountain View, California 94043.
Antimicrobial Agents and Chemotherapy
|December 1, 1993
Summary
A synthetic peptide derived from rabbit granulocytes, CAP18(106-142), demonstrates broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria. This peptide shows potential for treating bacterial sepsis, even in the presence of serum.
Area of Science:
- Biochemistry
- Microbiology
- Immunology
Background:
- Cationic antimicrobial protein of 18 kDa (CAP18) is found in rabbit granulocytes.
- The C-terminal 37 amino acids (CAP18(106-142)) form the lipopolysaccharide-binding domain.
- CAP18(106-142) exhibits broad antimicrobial activity.
Purpose of the Study:
- To investigate the antimicrobial activity of synthetic CAP18(106-142).
- To determine the structure-activity relationship of CAP18(106-142) fragments.
- To assess the activity of CAP18(106-142) in serum.
Main Methods:
- Synthesis of CAP18(106-142) and its fragments.
- Antimicrobial activity assays against Gram-positive and Gram-negative bacteria.
- Determination of 50% inhibitory concentrations (IC50).
- Activity assessment in the presence of serum.
Main Results:
- Synthetic CAP18(106-142) showed broad-spectrum activity against bacteria like Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
- IC50 values ranged from 20-100 nM for Gram-negative and 130-200 nM for Gram-positive bacteria.
- A 32-amino acid peptide derived from CAP18(106-142) retained high activity, while other fragments were inactive.
- CAP18(106-142) remained active in serum, unlike other granulocyte-derived antimicrobial peptides.
Conclusions:
- The lipopolysaccharide-binding domain of CAP18, specifically CAP18(106-142), possesses potent antimicrobial properties.
- Antimicrobial activity is dependent on the specific peptide structure.
- CAP18(106-142) is active in serum and may hold therapeutic potential for bacterial sepsis.