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Design of natterins-based peptides improves antimicrobial and antiviral activities

de Cena, Gabrielle L.; Tada, Dayane B.; Lucchi, Danilo B. M.; Santos, Tiago; Heras, Montserrat; Juliano, Maria; Torres Braconi, Carla

The biochemical analysis of animal venoms has been intensifying over the years, enabling the prediction of new molecules derived from toxins, harnessing the therapeutic potential of these molecules. From the venom of the fish Thalassophryne nattereri, using in silico methods for predicting antimicrobial and cell-penetrating peptides, two peptides from Natterins with promising characteristics were synthesized an...


The potential of peptide-based inhibitors in disrupting protein–protein interac...

Afonso, Alexandra L.; Cavaleiro, Catarina Tavares; Castanho, Miguel A. R. B.; Neves, Vera; Cavaco, Marco

Protein-protein interactions (PPIs) form an intricate cellular network known as the interactome, which is essential for various cellular processes, such as gene regulation, signal transduction, and metabolic pathways. The dysregulation of this network has been closely linked to various disease states. In cancer, these aberrant PPIs, termed oncogenic PPIs (OncoPPIs), are involved in tumour formation and prolifer...


What is the impact of thiamine deficiency on cognitive function in patients wit...

Teixeira, Joana; Pereira, Inês; Castanho, Miguel A. R. B.; Simões Do Couto, Frederico

Cognitive impairments are frequently observed in patients with Alcohol Use Disorder (AUD). Thiamine deficiency is often found in AUD patients and has been suggested as a possible cause of cognitive impairments. While thiamine deficiency is not consistently present in all AUD patients with cognitive deficits, thiamine is traditionally prescribed to patients with AUD to treat or prevent cognitive impairment. To b...


PepH3-modified nanocarriers for delivery of therapeutics across the blood-brain...

Szecskó, Anikó; Mészáros, Mária; Simões, Beatriz T.; Cavaco, Marco; Chaparro, Catarina; Porkoláb, Gergő; Castanho, Miguel A. R. B.; Deli, Mária A.

Background: Nanocarriers targeting the blood-brain barrier (BBB) are promising drug delivery systems to enhance the penetration of therapeutic molecules into the brain. Immunotherapy, particularly monoclonal antibodies designed to bind amyloid-beta peptides have become a promising strategy for Alzheimer's disease, but ensuring efficacy and safety is challenging and crucial for these therapies. Our aim was to de...


Antimigratory and antiproliferative effects of the brain‐targeted peptide conju...

Gonçalves, Catarina; Castanho, Miguel A. R. B.; Cavaco, Marco; Neves, Vera

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype affecting mostly younger women with a poor 5-year overall survival. It is characterized by a high metastization rate, particularly to the brain, where the blood-brain barrier (BBB) hinders the pharmaceuticals delivery. New anticancer drugs able to inhibit cell migration are required to effectively prevent the development of metastasis. ...


Machine learning assisted classification of staphylococcal biofilm maturity

van Dun, S.C.J.; Knol, R.; Silva-Herdade, Ana S.; Veiga, Ana Salomé; Castanho, Miguel A. R. B.; Nibbering, P.H.; Pijls, B.G.C.W.; van der Does, A.M.

An increasing incidence of device-related, biofilm-associated infections has been observed in clinical practice worldwide. In vitro biofilm models are essential to study these burdensome infections and to design and test potential new treatment approaches. However, there is considerable variation in in vitro biofilm models, and a generally accepted systematic description of biofilm maturity - apart from incubat...


Computationally-designed miniproteins showing neutralization activity against S...

Moreira, Pedro Daniel Martins; Parada, Mariana; Fernandes, Bárbara; Buga, Carolina C.; Teixeira, Rita I.; Oliveira, Christine; Buckley, Stephen Michael

As the COVID-19 pandemic demonstrated, the need for robust antiviral therapies against SARS-CoV-2 remains substantial. A promising strategy to meet this demand is through the development of proteins tailored for enhanced binding affinity to crucial viral targets, such as epitopes located on their fusion proteins. Among these targets is the Spike proteins receptor binding domain (RBD), which interacts with the h...


A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic ...

Fonseca-Gomes, João; Costa-Coelho, Tiago; Ferreira-Manso, Mafalda; Inteiro-Oliveira, Sara; Vaz, Sandra H.; Alemãn-Serrano, Nuno

In Alzheimer's disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology seve...


The use of a selective, nontoxic dual-acting peptide for breast cancer patients...

Cavaco, Marco; Pérez-Peinado, Clara; Valle, Javier; Silva, Rúben; Gano, Lurdes; Correia, João D. G.; Andreu, David; Castanho, Miguel A. R. B.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of commonly targeted receptors. Unspecific chemotherapy is currently the main therapeutic option, with poor results. Another major challenge is the frequent appearance of brain metastasis (BM) associated with a significant decrease in patient overall survival. The treatment of BM is even more challenging due to the presen...


Repurposing anti-cancer porphyrin derivative drugs to target SARS-CoV-2 envelope

Mendonça, Diogo A.; Cadima Couto, Carla Iris; Buga, Carolina C.; Arnaut, Zoe A.; Schaberle, Fabio A.; Arnaut, Luis G.; Castanho, Miguel A. R. B.

Antiviral medicines to treat COVID-19 are still scarce. Porphyrins and porphyrin derivatives (PDs) usually present broad-spectrum antiviral activity with low risk of resistance development. In fact, some PDs are clinicall approved to be used in anti-cancer photodynamic therapy and repurposing clinically approved PDs might be an alternative to treat COVID-19. Here, we characterize the ability of temoporfin, vert...


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