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What drives an amyloid protein precursor from an amyloidogenic to a native-like...
Quintas, AlexandreConformational disorders such as Alzheimer’s, Parkinson’s, familial amyloidotic polyneuropathy and spongiform encephalopaties are a consequence of protein misfolding and aggregation predominantly in the form of amyloid fibrils. These pathologies represent a major health problem, which most probably will overwhelm the health systems of developed countries in the near future. Significant progress has been made re...
An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and ...
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...
Evolution of the human immunodeficiency virus type 2 envelope in the first year...
Rocha, Cheila; Calado, Rita; Borrego, Pedro; Marcelino, José Maria; Bártolo, Inês; Rosado, Lino; Cavaco-Silva, Patrícia; Perpétua, Gomes"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 ...
Circular dichroism of anthocyanidin 3-glucoside self-aggregates
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 ex...
Insights into the molecular mechanism of protein native-like aggregation upon m...
Oliveira, Luís M. A.; Gomes, Ricardo A.; Yang, Dennis; Família, Carlos; Lages, Ana; Coelho, Ana V.; Murphy, Regina M.; Quintas, Alexandre"Protein glycation induces structural and stability changes that impair protein function, and is associated with several human neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and Familial Amyloidotic Polyneuropathy. Recently we have shown that methylglyoxal induces and stabilizes the formation of small native-like aggregates in the amyloidogenic protein insulin and the same was prev...
Resistance to antibody neutralization in HIV-2 infection occurs in late stage d...
Marcelino, José Maria; Borrego, Pedro; Nilsson, Charlotta; Família, Carlos; Barroso, Helena; Maltez, Fernando; Doroana, Manuela; Antunes, FranciscoObjectives: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients. ; Methods: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma IgG antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor usage...
Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Unde...
Barroso, Helena; Borrego, Pedro; Bártolo, Inês; Marcelino, José Maria; Família, Carlos; Quintas, Alexandre; Taveira, NunoBackground: Unlike in HIV-1 infection, the majority of HIV-2 patients produce broadly reactive neutralizing antibodies, control viral replication and survive as elite controllers. The identification of the molecular, structural and evolutionary footprints underlying these very distinct immunological and clinical outcomes may lead to the development of new strategies for the prevention and treatment of HIV infec...
Insulin glycation by methylglyoxal results in native-like aggregation and inhib...
Oliveira, Luis MA; Lages, Ana; Gomes, Ricardo A; Neves, Henrique; Família, Carlos; Coelho, Ana V; Quintas, AlexandreBackground: Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair p...
Fold-unfold transitions in the selectivity and mechanism of action of the N-ter...
Domingues, Marco M.; Lopes, Sílvia C. D. N.; Santos, Nuno C.; Quintas, Alexandre; Castanho, Miguel A. R. B.© 2009 by the Biophysical Society ; Septic or endotoxic shock is a common cause of death in hospital intensive care units. In the last decade numerous antimicrobial peptides and proteins have been tested in the search for an efficient drug to treat this lethal disease. Now in phase III clinical trials, rBPI21, a recombinant N-terminal fragment of the bactericidal/permeability-increasing protein (BPI), is a pro...
Estrutura e função de proteínas
Quintas, Alexandre; Ascenso, Carla; Abreu, Rui M.V.; Família, CarlosAs proteínas executam e controlam praticamente todas as funções nos sistemas biológicos, devendo a sua eficiência a milhares de milhões de anos de evolução na relação estrutura-função. Os factores que mais contribuem para a importância das proteínas nos sistemas biológicos são a capacidade de gerar superfícies complexas e cavidades específicas ao adquirirem a sua estrutura tridimensional, e de serem sistemas di...
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