BMB Reports
- Volume 32 Issue 1
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- Pages.12-19
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- 1999
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- 1976-670X(eISSN)
Synthesis and Characterization of GGN4 and its Tryptophan Substituted Analogue Peptides
- Kim, Se-Ha (Dept. of Life Science, K-JIST) ;
- Kim, Ji-Young (KRIBB, KIST) ;
- Lee, Byeong-Jae (Laboratory of Molecular Genetics, Institute for Molecular Biology and Genetics, Seoul National University) ;
- Kim, Soon-Jong (Department of Chemistry, Mokpo National University)
- Published : 1999.01.31
Abstract
Gaegurin 4 (GGN4), a broad-spectrum antibiotic, is a 37-amino acid peptide isolated from the Korean frog, Rana rugosa. In this study, we have chemically synthesized and purified GGN4 analogues where the C-terminal portion is truncated and/or substituted with tryptophan. These peptides show significantly different biological activities depending on the location of tryptophan and the number of amino acids truncated from the C-terminal end. While deletion of 9 amino acids from the C-terminal seems to be marginally tolerable in maintaining the antimicrobial activity, further deletion of up to 14 amino acid residues decreases the potency by more than 60-fold towards Gram-positive, and 10-fold towards Gram-negative, bacteria. Surprisingly, the reduced activity of the shorter peptide can be completely restored by a single substitution of aspartic acid 16 to tryptophan 16 (D16W). Also, the truncation seems to decrease the specificity of antibiotic activity more towards Gram-positive than towards Gram-negative bacteria studied. These data suggest a partial role of the C-terminal region in determining the binding specificity and the activity of peptides upon binding to their target cell membranes.
Keywords
- Deletion mutant;
- Gaegurin 4 (GGN4);
- Hemolysis;
- Minimum inhibitory concentration (MIC);
- Tryptophan substitution