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Enhanced Amphiphilic Profile of a Short β-Stranded Peptide Improves Its Antimicrobial Activity

Manzo, Giorgia; Scorciapino, Mariano A.; Wadhwani, Parvesh; Bürck, Jochen; Montaldo, Nicola Pietro; Pintus, Manuela; Sanna, Roberta; Casu, Mariano; Giuliani, Andrea; Pirri, Giovanna; Luca, Vincenzo; Ulrich, Anne S.; Rinaldi, Andrea C.

SB056 is a novel semi-synthetic antimicrobial peptide with a dimeric dendrimer scaffold. Active against both Gram-negative and -positive bacteria, its mechanism has been attributed to a disruption of bacterial membranes. The branched peptide was shown to assume a β- stranded conformation in a lipidic environment. Here, we report on a rational modification of the original, empirically derived linear peptide sequence [WKKIRVRLSA-NH$_{2}$, SB056-lin]. We interchanged the first two residues [KWKIRVRLSA-NH$_{2}$, β-SB056-lin] to enhance the amphipathic profile, in the hope that a more regular β-strand would lead to a better antimicrobial performance. MIC values confirmed that an enhanced amphiphilic profile indeed significantly increases activity against both Gram-positive and -negative strains. The membrane binding affinity of both peptides, measured by tryptophan fluorescence, increased with an increasing ratio of negatively charged/zwitterionic lipids. Remarkably, β- SB056-lin showed considerable binding even to purely zwitterionic membranes, unlike the original sequence, indicating that besides electrostatic attraction also the amphipathicity of the peptide structure plays a fundamental role in binding, by stabilizing the bound state. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/110101011
Veröffentlicht am 17.01.2018
DOI: 10.1371/journal.pone.0116379
Zitationen: 36
Web of Science
Zitationen: 36
Zitationen: 36
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2015
Sprache Englisch
Identifikator ISSN: 1932-6203
KITopen-ID: 110101011
HGF-Programm 47.02.02 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IBG-2
Weitere HGF-Programme 56.98.01 (POF III, LK 01) Betrieb in MML
Erschienen in PLoS one
Verlag Public Library of Science (PLoS)
Band 10
Seiten 1-18
Nachgewiesen in Dimensions
Web of Science
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