Probing coiled-coil assembly by paramagnetic NMR spectroscopy.

Here a new method to determine the oligomeric state and orientation of coiled-coil peptide motifs is described. Peptides K and E, which are designed to form a parallel heterodimeric complex in aqueous solution, were labeled with the aromatic amino acids tryptophan and tyrosine on the C-terminus respectively as 'fingerprint' residues. One of the peptides was also labeled with the paramagnetic probe MTSL.

Coiled-coil peptide motifs as thermoresponsive valves for mesoporous silica nanoparticles.

Coiled-coil peptide motifs were used as thermo-responsive valves for mesoporous silica nanoparticles (MSNs). The controlled release of a model drug as a function of temperature was demonstrated.

LP-211 is a brain penetrant selective agonist for the serotonin 5-HT(7) receptor.

We have determined the pharmacological profile of the new serotonin 5-HT(7) receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211). Radioligand binding assays were performed on a panel of 5-HT receptor subtypes. The compound was also evaluated in vivo by examining its effect on body temperature regulation in mice lacking the 5-HT(7) receptor (5-HT(7)(-/-)) and their 5-HT(7)(+/+) sibling controls.

Novel tricyclic Delta(2)-isoxazoline and 3-oxo-2-methyl-isoxazolidine derivatives: synthesis and binding affinity at neuronal nicotinic acetylcholine receptor subtypes.

A group of novel tricyclic Delta(2)-isoxazolines (4b, 5b, 7a-b, and 8a-b) and 3-oxo-isoxazolidines (6a-b and 9a-b), structurally related to cytisine or norferruginine, was prepared through 1,3-dipolar cycloadditions involving suitable olefins and bromonitrile oxide. The target compounds were assayed at alpha4beta2 and alpha7 neuronal acetylcholine receptors (nAChRs). The results of competition binding experiments indicated for the new derivatives a reduction of the affinity at the alpha4beta2 subtype in comparison with the reference molecules, coupled with an overall negligible affinity at the alpha7 subtype.

The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by alpha-synuclein or amyloid-beta (1-42) peptide.

Human sirtuins are a family of seven conserved proteins (SIRT1-7). The most investigated is the silent mating type information regulation-2 homolog (SIRT1, NM_012238), which was associated with neuroprotection in models of polyglutamine toxicity or Alzheimer's disease (AD) and whose activation by the phytocompound resveratrol (RES) has been described. We have examined the neuroprotective role of RES in a cellular model of oxidative stress, a common feature of neurodegeneration.