Structure‐activity relationship of Trp‐containing analogs of the antimicrobial peptide gomesin |
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Authors: | Tatiana M Domingues Marcus V Buri Sirlei Daffre Patricia T Campana Karin A Riske Antonio Miranda |
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Institution: | 1. Department of Biophysics, Federal University of Sao Paulo, , Sao Paulo, 04044‐020 Brazil;2. Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, , Brazil, 05508‐900;3. School of Arts, Sciences and Humanities, University of Sao Paulo, , Sao Paulo, Brazil, 03828‐000 |
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Abstract: | Gomesin (Gm) has a broad antimicrobial activity making it of great interest for development of drugs. In this study, we analyzed three Gm analogs, Trp1]‐Gm, Trp7]‐Gm, and Trp9]‐Gm, in an attempt to gain insight into the contributions of different regions of the peptide sequence to its activity. The incorporation of the tryptophan residue in different positions has no effect on the antimicrobial and hemolytic activities of the Gm analogs in relation to Gm. Spectroscopic studies (circular dichroism, fluorescence and absorbance) of Gm and its analogs were performed in the presence of SDS, below and above its critical micelle concentration (CMC) (~8 mM), in order to monitor structural changes induced by the interaction with this anionic surfactant (0–15 mM). Interestingly, we found that the analogs interact more strongly with SDS at low concentrations (0.3‐6.0 mM) than close to or above its CMC. This suggests that SDS monomers are able to cover the whole peptide, forming large detergent‐peptide aggregates. On the other hand, the peptides interact differently with SDS micelles, inserting partially into the micelle core. Among the peptides, Trp in position 1 becomes more motionally‐restricted in the presence of SDS, probably because this residue is located at the N‐terminal region, which presents higher conformational freedom to interact stronger with SDS molecules. Trp residues in positions 7 and 9, close to and in the region of the turn of the molecule, respectively, induced a more constrained structure and the compounds cannot insert deeper into the micelle core or be completely buried by SDS monomers. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. |
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Keywords: | gomesin antimicrobial peptide fluorescence circular dichroism absorbance |
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