A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Claudia Monteiro (Author) Other; Marina Pinheiro (Author) Other; Mariana Fernandes (Author) Other; Silvia Maia (Author) Other; Catarina L Seabra (Author) Other; Frederico Ferreira da Silva (Author) Other; Salette Reis (Author) FFUP; Paula Gomes (Author) FCUP; Cristina C L Martins (Author) Other

Journal

Title: Molecular Pharmaceutics

Vol. 12

Pages: 2904-2911

ISSN: 1543-8384

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 21 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-00G-J9Y

DOI: 10.1021/acs.molpharmaceut.5b00113

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific