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Title: Influence of the length and charge on the activity of alpha-helical amphipathic antimicrobial peptides
Author: Gagnon, Marie-Claude
Strandberg, Erik
Grau-Campistany, Ariadna
Wadhwani, Parvesh
Reichert, Johannes
Buerck, Jochen
Rabanal Anglada, Francesc
Auger, Michele
Paquin, Jean-Francois
Ulrich, Anne S.
Keywords: Pèptids
Membranes (Biologia)
Membranes (Biology)
Issue Date: 21-Mar-2017
Publisher: American Chemical Society
Abstract: Hydrophobic mismatch is important for pore forming amphipathic antimicrobial peptides, as demonstrated recently [Grau-Campistany, A., et al. (2015) Sci. Rep. 5, 9388]. A series of different length peptides have been generated with the heptameric repeat sequence KIAGKIA, called KIA peptides, and it was found that only those helices sufficiently long to span the hydrophobic thickness of the membrane could induce leakage in lipid vesicles; there was also a clear length dependence of the antimicrobial and hemolytic activities. For the original KIA sequences, the cationic charge increased with peptide length. The goal of this work is to examine whether the charge also has an effect on activity; hence, we constructed two further series of peptides with a sequence similar to those of the KIA peptides, but with a constant charge of +7 for all lengths from 14 to 28 amino acids. For both of these new series, a clear length dependence similar to that of KIA peptides was observed, indicating that charge has only a minor influence. Both series also showed a distinct threshold length for peptides to be active, which correlates directly with the thickness of the membrane. Among the longer peptides, the new series showed activities only slightly lower than those of the original KIA peptides of the same length that had a higher charge. Shorter peptides, in which Gly was replaced with Lys, showed activities similar to those of KIA peptides of the same length, but peptides in which Ile was replaced with Lys lost their helicity and were less active.
Note: Versió postprint del document publicat a:
It is part of: Biochemistry, 2017, vol. 56, num. 11, p. 1680-1695
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ISSN: 0006-2960
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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