| Title |
Rational modification of a dendrimeric peptide with antimicrobial activity: consequences on membrane-binding and biological properties
|
|---|---|
| Published in |
Amino Acids, November 2015
|
| DOI | 10.1007/s00726-015-2136-5 |
| Pubmed ID | |
| Authors |
Giovanna Batoni, Mariano Casu, Andrea Giuliani, Vincenzo Luca, Giuseppantonio Maisetta, Maria Luisa Mangoni, Giorgia Manzo, Manuela Pintus, Giovanna Pirri, Andrea C. Rinaldi, Mariano A. Scorciapino, Ilaria Serra, Anne S. Ulrich, Parvesh Wadhwani |
| Abstract |
Peptide-based antibiotics might help containing the rising tide of antimicrobial resistance. We developed SB056, a semi-synthetic peptide with a dimeric dendrimer scaffold, active against both Gram-negative and Gram-positive bacteria. Being the mechanism of SB056 attributed to disruption of bacterial membranes, we enhanced the amphiphilic profile of the original, empirically derived sequence [WKKIRVRLSA-NH2] by interchanging the first two residues [KWKIRVRLSA-NH2], and explored the effects of this modification on the interaction of peptide, both in linear and dimeric forms, with model membranes and on antimicrobial activity. Results obtained against Escherichia coli and Staphylococcus aureus planktonic strains, with or without salts at physiological concentrations, confirmed the added value of dendrimeric structure over the linear one, especially at physiological ionic strength, and the impact of the higher amphipathicity obtained through sequence modification on enhancing peptide performances. SB056 peptides also displayed intriguing antibiofilm properties. Staphylococcus epidermidis was the most susceptible strain in sessile form, notably to optimized linear analog lin-SB056-1 and the wild-type dendrimer den-SB056. Membrane affinity of all peptides increased with the percentage of negatively charged lipids and was less influenced by the presence of salt in the case of dendrimeric peptides. The analog lin-SB056-1 displayed the highest overall affinity, even for zwitterionic PC bilayers. Thus, in addition to electrostatics, distribution of charged/polar and hydrophobic residues along the sequence might have a significant role in driving peptide-lipid interaction. Supporting this view, dendrimeric analog den-SB056-1 retained greater membrane affinity in the presence of salt than den-SB056, despite the fact that they bear exactly the same net positive charge. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 50 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 16 | 32% |
| Student > Master | 9 | 18% |
| Researcher | 5 | 10% |
| Student > Bachelor | 5 | 10% |
| Other | 2 | 4% |
| Other | 3 | 6% |
| Unknown | 10 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 20% |
| Agricultural and Biological Sciences | 9 | 18% |
| Chemistry | 7 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 8% |
| Immunology and Microbiology | 4 | 8% |
| Other | 3 | 6% |
| Unknown | 13 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 November 2015.
All research outputs
#20,297,343
of 22,834,308 outputs
Outputs from Amino Acids
#1,285
of 1,520 outputs
Outputs of similar age
#324,746
of 387,438 outputs
Outputs of similar age from Amino Acids
#22
of 27 outputs
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