Browsing by Author "Quintas, Alexandre"
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- 2-Phenoxyethanol derivatization in ink dating determinationPublication . Leal, Teresa Argente; Ferreira, Carla; Quintas, Alexandre; Bernardo, Alexandra
- An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and HIV-2 fusion inhibitor activityPublication . Borrego, Pedro; Calado, Rita; Marcelino, José M.; Pereira, Patrícia; Quintas, Alexandre; Barroso, Helena; Taveira, Nuno"Objectives: To produce new fusion inhibitor peptides for HIV-1 and HIV-2 based on ancestral envelope sequences. Methods: HIV-2/simian immunodeficiency virus (SIV) ancestral transmembrane protein sequences were reconstructed and ancestral peptides were derived from the helical region 2 (HR2). The activity of one ancestral peptide (named P3) was examined against a panel of HIV-1 and HIV-2 primary isolates in TZM-bl cells and peripheral blood mononuclear cells and compared to T-20. Peptide secondary structure was analyzed by circular dichroism. Resistant viruses were selected and resistance mutations were identified by sequencing the env gene. Results: P3 has 34 residues and overlaps the N-terminal pocket-binding region and heptad repeat core of HR2. In contrast to T-20, P3 forms a typical a-helical structure in solution, binds strongly to the transmembrane protein, and potently inhibits both HIV-2 (mean IC50, 63.8 nmol/l) and HIV-1 (11 nmol/l) infection, including T-20-resistant isolates. The N43K mutation in the HR1 region of HIV-1 leads to 120-fold resistance to P3 indicating that the HR1 region in transmembrane glycoprotein is the target of P3. No HIV-2-resistant mutations could be selected by P3 suggesting that the genetic barrier to resistance is higher in HIV-2 than in HIV-1. HIV-1-infected patients presented significantly lower P3-specific antibody reactivity compared to T-20. Conclusion: P3 is an HIV-2/SIV ancestral peptide with low antigenicity, high stability, and potent activity against both HIV-1, including variants resistant to T-20, and HIV-2. Similar evolutionary biology strategies should be explored to enhance the production of antiviral peptide drugs, microbicides, and vaccines."
- Analysis of questioned documents on Egas Moniz Forensic and Psychological Sciences LaboratoryPublication . Leal, Teresa Argente; Mourato, Manuel; Cunha, José Abrantes da; Quintas, Alexandre
- Assessing the content of a package of SGT-151 sold onlinePublication . Luzio, Ana; Couceiro, Joana; Ferreira, Carla; Quintas, Alexandre
- A biophysical perspective on the unexplored mechanisms driving Parkinson’s disease by amphetamine-like stimulantsPublication . Ferreira, Carla; Couceiro, Joana; Tenreiro, Sandra; Quintas, Alexandre
- Circular dichroism of anthocyanidin 3-glucoside self-aggregatesPublication . Gavara, Raquel; Petrov, Vesselin; Quintas, Alexandre; Pina, Fernando"Self-association constants for the flavylium cations of the six most common anthocyanidin 3-glucosides were determined by circular dichroism (CD) and UV–Vis spectroscopy. Along with previous 1H NMR results, all measurements were consistent with a monomer–dimer model. The CD spectra of the antho-cyanidin 3-glucosides were similar to the analogues 3,5-diglucosides. All dimers of the anthocyanidin 3-glucosides exhibited left-handed CD signals, with petunidin-3-glucoside and myrtillin having the most intense signals. In addition, the magnitude of the molar ellipticity, [h], was generally higher for the 3-glucosides than for the 3,5-diglucosides. For all six anthocyanins studied, the CD absorption spectra of their dimers showed evidence of the splitting of the monomer absorption into lower (J) and higher (H) energy bands. The angle and the distance between the dipolar moments of the two monomers comprising the dimer were obtained from the lower energy absorption band. While the angle was more or less similar in all six dimers, the separation distance between the monomer dipole moments differed dramatically. The intensity of the CD signal displayed a linear dependence with the inverse square of the dipole moment distances."
- Development of green approaches for preconcentration of local anesthetics in biological matricesPublication . Pereira, Joana; Rocha, Daniela C.; Neng, Nuno R.; Torres, M. Edite; Quintas, Alexandre; Ahmad, Samir M.Poster presented at the CQE Days - 5º encontro anual do Centro de Química Estrutural do Instituto Superior Técnico da Universidade de Lisboa. Lisboa, 25-26 may 2023
- Development of green methodologies for pre-concentration of local anaesthetics in biological matricesPublication . Pereira, Joana; Rocha, Daniela C.; Neng, Nuno R.; Torres, M. Edite; Quintas, Alexandre; Ahmad, Samir M.Poster presented at the 6th International Congress of CiiEM—Immediate and Future Challenges to Foster One Health. Monte de Caparica, 5-7 july 2023
- Evaluation of toxic impact of the synthetic cannabinoids JWH-018 and its N-(3-hydroxypentyl) metabolite on human cell linesPublication . Couceiro, Joana; Sultan, Haider; Duranovic, Smilja; Bell, Suzanne; Quintas, Alexandre
- Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody responsePublication . Rocha, Cheila; Calado, Rita; Borrego, Pedro; Marcelino, José Maria; Bártolo, Inês; Rosado, Lino; Cavaco-Silva, Patrícia; Perpétua, Gomes; Família, Carlos; Quintas, Alexandre; Skar, Helena; Leitner, Thomas; Barroso, Helena; Taveira, Nuno"Background: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results: CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis."
