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The major components of neuritic plaques found in Alzheimer disease (AD) are peptides known as amyloid beta-peptides (Abeta), which derive from the proteolitic cleavage of the amyloid precursor proteins. In vitro Abeta may undergo a conformational transition from a soluble form to aggregated, fibrillary beta-sheet structures, which seem to be neurotoxic.(More)
BACKGROUND Tyr-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) and Tyr-Tic-Ala were the first peptides with delta opioid antagonist activity lacking Phe, considered essential for opioid activity based on the N-terminal tripeptide sequence (Tyr-D-Xaa-Phe) of amphibian skin opioids. Analogs were then designed to restrain the rotational flexibility of(More)
Deficiency of the small mitochondrial protein frataxin causes Friedreich's ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe-S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and(More)
Understanding the factors that determine protein stability is interesting because it directly reflects the evolutionary pressure coming from function and environment. Here, we have combined experimental and computational methods to study the stability of IscU, a bacterial scaffold protein highly conserved in most organisms and an essential component of the(More)
Sweet tasting proteins interact with the same receptor that binds small molecular weight sweeteners, the T1R2-T1R3 G-protein coupled receptor, but the key groups on the protein surface responsible for the biological activity have not yet been identified. I propose that sweet proteins, contrary to small ligands, do not bind to the 'glutamate-like' pocket but(More)
Protein aggregation constitutes a constant threat for the living cell as is demonstrated by the several pathologies in which the mechanisms to prevent it fail. It is therefore a question of increasing importance to understand in detail the defence strategies. Here we discuss how molecular interactions can represent a general strategy to prevent aggregation.(More)
Conformational studies of enkephalins are hampered by their high flexibility which leads to mixtures of quasi-isoenergetic conformers in solution and makes NOEs very difficult to detect in NMR spectra. In order to improve the quality of the NMR data, Leu-enkephalin was synthesized with 15N-labelled uniformly on all amide nitrogens and examined in a viscous(More)
Elucidation of the molecular bases of sweet taste is very important not only for its intrinsic biological significance but also for the design of new artificial sweeteners. Up to few years ago design was complicated by the common belief that different classes of sweet compounds, notably sweet proteins, might interact with different receptors altogether. The(More)
Met5-enkephalin was studied in 1 mM solutions in 2H2O at room temperature and in a cryoprotective mixture (DMSOd6/2H2O, mole fraction of DMSO 0.49) in the temperature range 265-298 K. Small positive effects were observed between the ortho and meta protons of Tyr in aqueous solution at room temperature. Intraresidue effects can be made strong and negative by(More)
Nociceptin (NC) and some of its fragments as well as nociceptin-(1-13)-peptide amide [NC- (1-13)-NH2] and a series of its analogues were prepared and tested in the mouse vas deferens in an attempt to identify the sequences involved in the activation (message) and in the binding (address) of nociceptin to its receptor. The NC receptor that inhibits the(More)