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Phosphate-dependent aggregation of [KL]$_{n}$ peptides affects their membranolytic activity

Strandberg, E.; Schweigardt, F.; Wadhwani, P.; Bürck, J.; Reichert, J.; Cravo, H. L. P.; Burger, L.; Ulrich, A. S.

Abstract:
In this study, we investigate how the length of amphiphilic β-sheet forming peptides affects their interaction with membranes. Four polycationic model peptides with lengths from 6 to 18 amino acids were constructed from simple Lys-Leu repeats, giving [KL]$_{n=3,5,7,9}$. We found that (1) they exhibit a pronounced antimicrobial activity with an intriguing length dependent maximum for [KL]$_{5}$ with 10 amino acids; (2) their hemolytic effect, on the other hand, increases steadily with peptide length. CD analysis (3) and TEM (4) show that all peptides-except for the short [KL]$_{3}$-aggregate into amyloid-like fibrils in the presence of phosphate ions, which in turn has a critical effect on the results in (1) and (2). In fact, (5) vesicle leakage reveals an intrinsic membrane-perturbing activity (at constant peptide mass) of [KL]$_{5}$ > [KL]$_{9}$ > [KL]7 in phosphate buffer, which changes to [KL]$_{5}$ ≈ [KL]$_{7}$ ≈ [KL]$_{9}$ in PIPES. A specific interaction with phosphate ions thus explains the subtle balance between two counteracting effects: phosphate-induced unproductive pre-aggregation in solution versus monomeric membrane binding and vigorous lipid perturbation due to self-assembly of the bound peptides within the bilayer. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000122956
Veröffentlicht am 27.08.2020
Originalveröffentlichung
DOI: 10.1038/s41598-020-69162-0
Scopus
Zitationen: 1
Web of Science
Zitationen: 1
Dimensions
Zitationen: 2
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000122956
HGF-Programm 47.02.02 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IBG-2
Erschienen in Scientific reports
Verlag Nature Research
Band 10
Heft 1
Seiten Art.Nr. 12300
Vorab online veröffentlicht am 23.07.2020
Nachgewiesen in Dimensions
Web of Science
Scopus
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