Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry
PBN-AR
Instytucja
Instytut Chemii Organicznej Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
MOLECULES
ISSN
1420-3049
EISSN
Wydawca
MDPI AG
DOI
URL
Rok publikacji
2013
Numer zeszytu
6
Strony od-do
7120-7120
Numer tomu
18
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Słowa kluczowe
en
dendrimers; peptides; amphiphilic surface; antimicrobial; high salt conditions; circular dichroism; phospholipids; ESI-MS; collision-induced dissociation (CID)
Streszczenia
Język
en
Treść
A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn) core were synthesized and characterized by ESI-MS, 1H-, 13C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected as a result of an increased charge, higher branching and variable lipophilicity of the residues located at the C-terminus. Minimal inhibitory concentration (MIC) values indicated that the selected dendrimers were not sensitive to the physiological concentration of Na+ and K+ ions (100 mM), but expressed reduced potency at 10 mM concentration of Mg2+ and Ca2+ ions. Circular dichroism (CD) curves measured under various conditions revealed structure and solvent-dependent curve evolution. ESI-MS studies of gas-phase interactions between selected dendrimers and both anionic (DMPG) and neutral (DMPC) phospholipids revealed the presence of variously charged dendrimer/phospholipid aggregates with 1:1 to 1:5 stoichiometry. The collision-induced fragmentation (CID) of the most abundant [dendrimer/phospholipid]2+ ions of the 1:1 stoichiometry demonstrated that the studied dendrimers formed stronger complexes with anionic DMPG. Both phospholipids have higher affinity towards dendrimers with a more compact structure. Higher differences in CID energy necessary for dissociation of 50% of the complex formed by dendrimers with DMPG vs. DMPC (DCID50) correlate with a lower hemotoxicity. Mass spectrometry results suggest that for a particular group of compounds the DCID50 might be one of the important factors explaining selectivity of antimicrobial peptides and their branched analogs targeting the bacterial membrane. Both circular dichroism and mass spectrometry studies demonstrated that dendrimers of Nα- and Nε-series possess a different conformation in solution and different affinity to model phospholipids, what might influence their specific microbicidal mechanism.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
644972
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