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Molecules 2013, 18(6), 7120-7144; doi:10.3390/molecules18067120
Article

Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry

1, 1, 1,* , 1, 1, 2, 2 and 1,*
Received: 9 April 2013; in revised form: 4 June 2013 / Accepted: 6 June 2013 / Published: 18 June 2013
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Abstract: 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.
Keywords: dendrimers; peptides; amphiphilic surface; antimicrobial; high salt conditions; circular dichroism; phospholipids; ESI-MS; collision-induced dissociation (CID) dendrimers; peptides; amphiphilic surface; antimicrobial; high salt conditions; circular dichroism; phospholipids; ESI-MS; collision-induced dissociation (CID)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Polcyn, P.; Zielinska, P.; Zimnicka, M.; Troć, A.; Kalicki, P.; Solecka, J.; Laskowska, A.; Urbanczyk-Lipkowska, Z. Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry. Molecules 2013, 18, 7120-7144.

AMA Style

Polcyn P, Zielinska P, Zimnicka M, Troć A, Kalicki P, Solecka J, Laskowska A, Urbanczyk-Lipkowska Z. Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry. Molecules. 2013; 18(6):7120-7144.

Chicago/Turabian Style

Polcyn, Piotr; Zielinska, Paulina; Zimnicka, Magdalena; Troć, Anna; Kalicki, Przemysław; Solecka, Jolanta; Laskowska, Anna; Urbanczyk-Lipkowska, Zofia. 2013. "Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry." Molecules 18, no. 6: 7120-7144.


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