Amyloid beta peptide (Abeta) aggregation leads to the senile plaque formation, a process that is strongly influenced by oxidative stress and is considered as the molecular basis of various neurodegenerative diseases, such as Alzheimer's disease (AD). Endogenous antioxidants or dietary derived compounds may down-regulate this process. In this study, the interaction of two antioxidants, oleuropein (OE) and melatonin (M), with Abeta is monitored through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The concerted application of these two analytical techniques provides new experimental evidence and residue-specific insights into the interacting Abeta peptide amino acids that are implicated in this process. Both antioxidant compounds interact in a similar way with the peptide and cause chemical shift variations. The most pronounced resonance changes have been observed for the 1H-15N signals of N-terminal region and Leu17-Phe20 residues, as monitored by NMR titration studies.

Infection of target host cells by the human immunodeficiency virus-1 (HIV-1) is a multi-step process involving a series of conformational changes in the viral gp120 and gp41 proteins. Gp120 binding to the main cell receptor, CD4, on the surface of cells expressing this molecule, and interaction with the cell chemokine receptors CCR5 and CXCR4, are among the key events for HIV-1 infection. These steps are crucial for the virus and offer potential therapeutic targets. For this reason, understanding the structure and the physicochemical characteristics of the gp120 in relation to these interactions has drawn much attention. This review article focuses on the biologically important V3 region of the gp120 and summarizes the functional role, the sequence variation and the conformational features of V3 peptides, which are important for co-receptor selectivity, specificity and interaction. Synthetic V3 peptides have been extensively studied by NMR spectroscopy and X-ray crystallography, in solution or in solid state, in their free or bound form, and valuable information was generated with the aim to be exploited in the design of new, effective inhibitors of HIV-1 infection. The features of the potential gp120 interacting sites on the two chemokine co-receptors, CCR5 and CXCR4, are also discussed, and co-receptor blocking molecules under clinical trial are also reported.

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The third variable (V3) loop is an important region of glycoprotein 120 (gp120) for many biological processes, as it contains the highly conserved GPGR sequence and it represents the binding site for human immunodeficiency virus 1 (HIV-1) antibodies and for CCR5 and CXCR4 host cell coreceptors. The interaction of the principal neutralizing determinant (PND) V3 with the chemokine receptor CCR5 N-terminal region has been reported to be crucial for HIV-1 infection. The goal of this study is to characterize the solution structures of three HIV-1 gp120 V3 subtype B peptides and their interaction with a nonsulfated N-terminal CCR5 peptide. NMR titration experiments revealed that the CCR5Nt-PND V3 interaction is dependent on the number of the positively charged V3 residues, which is in agreement with the observation that increase in positive charge in the V3 sequence correlates with the augmentation of the interaction. As expected for free peptides in solution, the peptides representing the PND V3 region of gp120 exhibit conformational flexibility, but they also exhibit a large number of NOEs which allowed convergence to a dominant conformation. The PND V3 peptides retain the U-turn conformation observed in the crystal structures of gp120 complexes independently of CCR5 presence. The interaction of different regions of the CCR5Nt peptide is gradually increasing proportionally to the positive charge increase in the V3 peptides. The data demonstrate that the PND V3 and CCR5Nt peptide sequences have propensities for interaction even in the absence of sulfated tyrosines and that their binding and selectivity is determined by simple electrostatic attraction mechanisms.

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