Please use this identifier to cite or link to this item:
https://hdl.handle.net/10216/82150
Author(s): | Claudia Monteiro Marina Pinheiro Mariana Fernandes Silvia Maia Catarina L Seabra Frederico Ferreira da Silva Salette Reis Paula Gomes Cristina C L Martins |
Title: | A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
Issue Date: | 2015 |
Abstract: | Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78. |
Subject: | Medicina básica Basic medicine |
Scientific areas: | Ciências médicas e da saúde::Medicina básica Medical and Health sciences::Basic medicine |
URI: | https://hdl.handle.net/10216/82150 |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | openAccess |
License: | https://creativecommons.org/licenses/by-nc/4.0/ |
Appears in Collections: | FCUP - Artigo em Revista Científica Internacional FFUP - Artigo em Revista Científica Internacional |
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