Publication
Lipid selectivity in novel antimicrobial peptides : implication on antimicrobial and hemolytic activity
| dc.contributor.author | Maturana, P. | |
| dc.contributor.author | Martinez, M. | |
| dc.contributor.author | Noguera, M. E. | |
| dc.contributor.author | Santos, N. C. | |
| dc.contributor.author | Disalvo, E. A. | |
| dc.contributor.author | Semorile, L. | |
| dc.contributor.author | Maffia, P. C. | |
| dc.contributor.author | Hollmann, A. | |
| dc.date.accessioned | 2018-05-07T15:53:06Z | |
| dc.date.available | 2018-05-07T15:53:06Z | |
| dc.date.issued | 2017 | |
| dc.description | © 2017 Elsevier B.V. All rights reserved | pt_PT |
| dc.description.abstract | Antimicrobial peptides (AMPs) are small cationic molecules that display antimicrobial activity against awide range of bacteria, fungi and viruses. For an AMP to be considered as a therapeutic option, it musthave not only potent antibacterial properties but also low hemolytic and cytotoxic activities [1]. Eventhough many studies have been conducted in order to correlate the antimicrobial activity with affinitytoward model lipid membranes, the use of these membranes to explain cytotoxic effects (especiallyhemolysis) has been less explored. In this context, we studied lipid selectivity in two related novel AMPs,peptide 6 (P6) and peptide 6.2 (P6.2). Each peptide was designed from a previously reported AMP, andspecific amino acid replacements were performed in an attempt to shift their hydrophobic momentor net charge. P6 showed no antimicrobial activity and high hemolytic activity, and P6.2 exhibited goodantibacterial and low hemolytic activity. Using both peptides as a model we correlated the affinity towardmembranes of different lipid composition and the antimicrobial and hemolytic activities. Our results fromsurface pressure and zeta potential assays showed that P6.2 exhibited a higher affinity and faster bindingkinetic toward PG-containing membranes, while P6 showed this behavior for pure PC membranes. Thefinal position and structure of P6.2 into the membrane showed an alpha-helix conversion, resulting in aparallel alignment with the Trps inserted into the membrane. On the other hand, the inability of P6 toadopt an amphipathic structure, plus its lower affinity toward PG-containing membranes seem to explainits poor antimicrobial activity. Regarding erythrocyte interactions, P6 showed the highest affinity towarderythrocyte membranes, resulting in an increased hemolytic activity. Overall, our data led us to concludethat affinity toward negatively charged lipids instead of zwitterionic ones seems to be a key factor thatdrives from hemolytic to antimicrobial activity. | pt_PT |
| dc.description.sponsorship | This work was supported by grants from Universidad Nacionalde Quilmes, Comisión de Investigaciones Científicas de la Provinciade Buenos Aires (CIC-BA), Agencia Nacional de Promocion Cientıficay Tecnologica (ANPCyT–MINCyT), PICT 2013-1481, PICT 2013-815,CONICET, Argentina; PIP-2014-11220130100383CO and Fundação para a Ciência e Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal). LS is a member of the Research Career of CIC-BA. AH, EAD and PCM are members of the Carrera del Investigador Cientıfico y Tecnologico (CONICET, Argentina). MM and MEN acknowledge fellowships from CONICET, PM has a fellowship from CIN (Consejo Interuniversitario Nacional, Argentina). | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Colloids and Surfaces B: Biointerfaces 153 (2017) 152–159 | pt_PT |
| dc.identifier.doi | doi.org/10.1016/j.colsurfb.2017.02.003 | pt_PT |
| dc.identifier.issn | 0927-7765 | |
| dc.identifier.uri | http://hdl.handle.net/10451/33208 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.relation.publisherversion | https://www.journals.elsevier.com/colloids-and-surfaces-b-biointerfaces | pt_PT |
| dc.subject | Antimicrobial peptides | pt_PT |
| dc.subject | Membrane affinity | pt_PT |
| dc.subject | Hemolysis | pt_PT |
| dc.title | Lipid selectivity in novel antimicrobial peptides : implication on antimicrobial and hemolytic activity | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 159 | pt_PT |
| oaire.citation.startPage | 152 | pt_PT |
| oaire.citation.title | Colloids and Surfaces B: Biointerfaces | pt_PT |
| oaire.citation.volume | 153 | pt_PT |
| rcaap.rights | restrictedAccess | pt_PT |
| rcaap.type | article | pt_PT |