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Quantitative analysis of molecular partition towards lipid membranes using surf...

Figueira, Tiago N.; Freire, João M.; Santos, Catarina Cunha; Heras, Montserrat; Gonçalves, João; Moscona, Anne; Porotto, Matteo; Veiga, Ana Salomé

Understanding the interplay between molecules and lipid membranes is fundamental when studying cellular and biotechnological phenomena. Partition between aqueous media and lipid membranes is key to the mechanism of action of many biomolecules and drugs. Quantifying membrane partition, through adequate and robust parameters, is thus essential. Surface Plasmon Resonance (SPR) is a powerful technique for studying ...


Quantitative analysis of molecular partition towards lipid membranes using surf...

Figueira, Tiago N.; Freire, João M.; Santos, Catarina Cunha; Heras, Montserrat; Gonçalves, João; Moscona, Anne; Porotto, Matteo; Veiga, Ana Salomé

Understanding the interplay between molecules and lipid membranes is fundamental when studying cellular and biotechnological phenomena. Partition between aqueous media and lipid membranes is key to the mechanism of action of many biomolecules and drugs. Quantifying membrane partition, through adequate and robust parameters, is thus essential. Surface Plasmon Resonance (SPR) is a powerful technique for studying ...


New potent membrane-targeting antibacterial peptides from viral capsid proteins

Dias, Susana A.; Freire, João M.; Pérez-Peinado, Clara; Domingues, Marco M.; Gaspar, Diana; Vale, Nuno; Gomes, Paula Gomes; Andreu, David

The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here...


Mechanisms of vesicular stomatitis virus inactivation by protoporphyrin ix, zin...

Oliveira, Christine Cruz; Almeida, Andreza F.; Freire, João M.; Caruso, Marjolly B.; Morando, Maria A.; Ferreira, Vivian N. S.

Virus resistance to antiviral therapies is an increasing concern that makes the development of broad-spectrum antiviral drugs urgent. Targeting of the viral envelope, a component shared by a large number of viruses, emerges as a promising strategy to overcome this problem. Natural and synthetic porphyrins are good candidates for antiviral development due to their relative hydrophobicity and pro-oxidant characte...


Rethinking the capsid proteins of enveloped viruses : multifunctionality from g...

Freire, João M.; Santos, Nuno C.; Veiga, Ana Salomé; Poian, Andrea T. da; Castanho, Miguel A. R. B.

Regardless of the debate on whether there is a place for viruses in the tree of life, it is consensual that they co-evolve with their hosts under the pressure of genome minimization. The abundance of multifunctional viral structural proteins is a consequence of this pressure. The molecular key to multifunctionality is the existence of intrinsically disordered domains together with ordered domains in the same pr...


Shifting gear in antimicrobial and anticancer peptides biophysical studies : fr...

Freire, João M.; Gaspar, Diana; Veiga, Ana Salomé; Castanho, Miguel A. R. B.

Despite the intensive study on the mechanism of action of membrane-activemolecules such as antimicrobial and anticancer peptides, most of the biophysical work has been performed using artificial model systems, mainly lipid vesicles. The use of these systems allows full control of the experimental parameters, and to obtain molecular-level detail on the action of peptides, the correlation with biological action i...


Correlation between membrane translocation and analgesic efficacy in kyotorphin...

Serrano, Isa D.; Ramu, Vasanthakumar G.; Pinto, Antónia R. T.; Freire, João M.; Tavares, Isaura; Heras, Montserrat; Bardaji, Eduard R.

Amidated kyotorphin (L-Tyr-L-Arg-NH2; KTP-NH2) causes analgesia when systemically administered. The lipophilic ibuprofen-conjugated derivative of KTP-NH2 has improved analgesic efficacy. However, fast degradation by peptidases impacts negatively in the pharmacodynamics of these drugs. In this work, selected derivatives of KTP and KTP-NH2 were synthesized to combine lipophilicity and resistance to enzymatic degr...


Apoptotic human neutrophil peptide-1 anti-tumor activity revealed by cellular b...

Gaspar, Diana; Freire, João M.; Pacheco, Teresa R.; Barata, João T.; Castanho, Miguel A. R. B.

Cancer remains a major cause of morbidity and mortality worldwide. Although progress has been made regarding chemotherapeutic agents, new therapies that combine increased selectivity and efficacy with low resistance are still needed. In the search for new anticancer agents, therapies based on biologically active peptides, in particular, antimicrobial peptides (AMPs), have attracted attention for their decreased...


Nucleic acid delivery by cell penetrating peptides derived from dengue virus ca...

Freire, João M.; Veiga, Ana Salomé; Figueiredo, Inês Rego de; Torre, Beatriz G. de la; Santos, Nuno C.; Andreu, David; Poian, Andrea T. da

Cell penetrating peptides (CPPs) can be used as drug delivery systems for different therapeutic molecules. In this work two novel CPPs, pepR and pepM, designed from two domains of the dengue virus (DENV) capsid protein, were studied for their ability to deliver nucleic acids into cells as non-covalently bound cargo. Translocation studies were performed by confocal microscopy in HepG2, BHK and HEK cell lineages,...


The mechanisms and quantification of the selective permeability in transport ac...

Serrano, Isa D.; Freire, João M.; Carvalho, Miguel V.; Neves, Mafalda; Melo, Manuel N.; Castanho, Miguel A. R. B.

This paper addresses the mechanisms behind selective endothelial permeability and their regulations. The singular properties of each of the seven blood-tissues barriers. Then, it further revisits the physical, quantitative meaning of permeability, and the way it should be measured based on sound physical chemistry reasoning and methodologies. Despite the relevance of permeability studies one often comes across ...


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