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

Polcyn, Piotr; Zielińska, Paulina; Zimnicka, Magdalena; Troć, Anna; Kalicki, Przemysław; Solecka, Jolanta; Laskowska, Anna; Urbańczyk‐Lipkowska, Zofia

doi:10.3390/molecules18067120

Cited by 18 publications

(21 citation statements)

References 41 publications

(40 reference statements)

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“…We therefore chose the option to protect the susceptible points of proteolysis of the molecule. Other options may increase the stability such as polyethyleneglycol (PEG) [31], the use of lipids for drug delivery of the peptides [32], the use of nanoparticules in order to achieve a longer life time [33] or the use of dendrimers [34]. The mastoparan family is a very promising group of potential new drugs.…”

Section: Resultsmentioning

confidence: 99%

Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii

Vila-Farrés

López-Rojas

Pachón-Ibáñez

et al. 2015

European Journal of Medicinal Chemistry

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The treatment of some infectious diseases can currently be very challenging since the spread of multi-, extended- or pan-resistant bacteria has considerably increased over time. On the other hand, the number of new antibiotics approved by the FDA has decreased drastically over the last 30 years. The main objective of this study was to investigate the activity of wasp peptides, specifically mastoparan and some of its derivatives against extended-resistant Acinetobacter baumannii. We optimized the stability of mastoparan in human serum since the specie obtained after the action of the enzymes present in human serum is not active. Thus, 10 derivatives of mastoparan were synthetized. Mastoparan analogues (guanidilated at the N-terminal, enantiomeric version and mastoparan with an extra positive charge at the C-terminal) showed the same activity against Acinetobacter baumannii as the original peptide (2.7 μM) and maintained their stability to more than 24 h in the presence of human serum compared to the original compound. The mechanism of action of all the peptides was carried out using a leakage assay. It was shown that mastoparan and the abovementioned analogues were those that released more carboxyfluorescein. In addition, the effect of mastoparan and its enantiomer against A. baumannii was studied using transmission electron microscopy (TEM). These results suggested that several analogues of mastoparan could be good candidates in the battle against highly resistant A. baumannii infections since they showed good activity and high stability.

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Section: Resultsmentioning

confidence: 99%

Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii

Vila-Farrés

López-Rojas

Pachón-Ibáñez

et al. 2015

European Journal of Medicinal Chemistry

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“…In addition, dendrimer-bound siRNA was displaced by the polyanion heparin, suggesting that siRNA dissociation from the dendron inside the cell could be easily achieved. Moreover, all four dendrons were able to facilitate the uptake of FAM-siRNA and to produce a decrease in protein levels of a protein when specific siRNA was transfected into glioblastoma cells, providing grounds for its possible use as a transfectant reagent [43]. However, the most interesting feature of two of these dendrons (F4 and F11) is their toxicity against glioblastoma cells (both human and murine), while sparing other CNS cells such as astrocytes and neurons that share the anatomical space with glioblastoma cells during the course of the disease.…”

Section: Discussionmentioning

confidence: 99%

Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes

et al. 2016

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Glioblastomas are the most common malignant primary brain tumours in adults and one of the most aggressive and difficult-to-treat cancers. No effective treatment exits actually for this tumour and new therapeutic approaches are needed for this disease. One possible innovative approach involves the nanoparticle-mediated specific delivery of drugs and/or genetic material to glioblastoma cells where they can provide therapeutic benefits. In the present work, we have synthesised and characterised several second generation amphiphilic polylysine dendrons to be used as siRNA carriers. We have found that, in addition to their siRNA binding properties, these new compounds inhibit the proliferation of two glioblastoma cell lines while being nontoxic for non-tumoural central nervous system cells like neurons and glia, cell types that share the anatomical space with glioblastoma cells during the course of the disease. The selective toxicity of these nanoparticles to glioblastoma cells, as compared to neurons and glial cells, involves mitochondrial depolarisation and reactive oxygen species production. This selective toxicity, together with the ability to complex and release siRNA, suggests that these new polylysine dendrons might offer a scaffold in the development of future nanoparticles designed to restrict the proliferation of glioblastoma cells.

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“…This is due to the very limited number of studies reported on how these novel types of peptide-based dendrimers interact with model cellular membranes [23][24][25].…”

Section: Introductionmentioning

confidence: 93%

Antimicrobial peptide dendrimer interacts with phosphocholine membranes in a fluidity dependent manner: A neutron reflection study combined with molecular dynamics simulations

Lind

Darré

Domene

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The interaction mechanism of a novel amphiphilic antimicrobial peptide dendrimer, BALY, with model lipid bilayers was explored through a combination of neutron reflection and molecular dynamics simulations. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3-phos-phocholine (DPPC) lipid bilayers were examined at room temperature to extract information on the interaction of BALY with fluid and gel phases, respectively. Furthermore, a 1:4 mixture of POPC and DPPC was used as a model of a phase-separated membrane. Upon interaction with fluid membranes, BALY inserted in the distal leaflet and caused thinning and disordering of the headgroups. Membrane thinning and expansion of the lipid crosssectional area were observed for gel phase membranes, also with limited insertion to the distal leaflet. However, dendrimer insertion through the entire lipid tail region was observed upon crossing the lipid phase transition temperature of DPPC and in phase separated membranes. The results show clear differences in the interaction mechanism of the dendrimer depending on the lipid membrane fluidity, and suggest a role for lipid phase separation in promoting its antimicrobial activity.

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

Cited by 18 publications

References 41 publications

Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii

Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii

Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes

Antimicrobial peptide dendrimer interacts with phosphocholine membranes in a fluidity dependent manner: A neutron reflection study combined with molecular dynamics simulations

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