Helical versus Flat Bis-Ferrocenyl End-Capped Peptides: The Influence of the Molecular Skeleton on Redox Properties.

Despite the fact that peptide conjugates with a pendant ferrocenyl (Fc) have been widely investigated, bis-ferrocenyl end-capped peptides are rarely synthetized. In this paper, in addition to the full characterization of the Fc-CO-[L-Dap(Boc)]n-NH-Fc series, we report a comparison of the three series of bis-ferrocenyl homopeptides synthesized to date, to gain insights into the influence of α-amino isobutyric (Aib), 2,3-diamino propionic (Dap) and Cα,ß-didehydroalanine (ΔAla) amino acids on the peptide secondary structure and on the ferrocene redox properties. The results obtained by 2D NMR analysis and X-ray crystal structures, and further supported by electrochemical data, evidence different behaviors depending on the nature of the amino acid; that is, the formation of 310-helices or fully extended (2.05-helix) structures. In these foldamers, the orientation of the carbonyl groups in the peptide helix yields a macrodipole with the positive pole on the N-terminal amino acid and the negative pole on the C-terminal amino acid, so that oxidation of the Fc moieties takes place more or less easily depending on the orientation of the macrodipole moment as the peptide chain grows. Conversely, the fully extended conformation adopted by ΔAla flat peptides neither generates a macrodipole nor affects Fc oxidation. The utilization as electrochemical and optical (Circular Dichroism) probes of the two terminal Fc groups, bound to the same peptide chain, makes it possible to study the end-to-end effects of the positive charges produced by single and double oxidations, and to evidence the presence "exciton-coupled" CD among the two intramolecularly interacting Fc groups of the L-Dap(Boc) series.

Novel morpholine scaffolds as selective dopamine (DA) D3 receptor antagonists.

A new series of morpholine derivatives has been identified as selective DA D3 receptor antagonists; their in vitro profile and pharmacokinetic data are provided.

1,2,4-Triazolyl octahydropyrrolo[2,3-b]pyrroles: A new series of potent and selective dopamine D3 receptor antagonists.

A novel series of 1,2,4-triazolyl octahydropyrrolo[2,3-b]pyrroles showing high affinity and selectivity at the DA D3 receptor is reported here. Compounds endowed with high selectivity over the hERG channel were identified and their pharmacokinetic properties thoroughly analyzed. A few derivatives with appropriate developability characteristics were selected for further studies and progression along the screening cascade. In particular, derivative 60a, (DA D3 pKi=8.4, DA D2 pKi=6.0 and hERG fpKi=5.2) showed a balanced profile and further refinements are in progress around this molecule.

Flat, Cα,ß -Didehydroalanine Foldamers with Ferrocene Pendants: Assessing the Role of α-Peptide Dipolar Moments.

The foldamer field is continuously expanding as it allows to produce molecules endowed with 3D-structures and functions never observed in nature. We synthesized flat foldamers based on the natural, but non-coded, Cα,ß -didehydroalanine α-amino acid, and covalently linked to them two ferrocene (Fc) moieties, as redox probes. These conjugates retain the flat and extended conformation of the 2.05 -helix, both in solution and in the crystal state (X-ray diffraction). Cyclic voltammetry measurements agree with the adoption of the 2.05 -helix, characterized by a negligible dipole moment. Thus, elongated α-peptide stretches of this type are insulators rather than charge conductors, the latter being constituted by peptide α-helices. Also, our homo-tetrapeptide has a N-to-C length of about 18.2 Å, almost double than that (9.7 Å) of an α-helical α-tetrapeptide.

Synthesis and pharmacological characterization of 5-phenyl-2-[2-(1-piperidinylcarbonyl)phenyl]-2,3-dihydro-1H-pyrrolo[1,2-c]imidazol-1-ones: a new class of Neuropeptide S antagonists.

A new class of selective NPS antagonist was developed starting from a commercially available product identified by screening activities. Experimental NMR observations and computational experiments allowed the discovery of a new class of derivatives. 5-Phenyl-2-[2-(1-piperidinylcarbonyl)phenyl]-2,3-dihydro-1H-pyrrolo[1,2-c]imidazol-1-one represents a new lead compound in the NPS antagonist field.

The transmission of racial attitudes within the family.

Previous literature based on self-report measures has not found a clear relationship between the ethnic attitudes of White parents and those of their children. In particular, no study has evidenced such a relationship in the case of preschool children. In the present study, the authors measured parents' implicit and explicit racial attitudes as well as the racial attitudes of their 3- to 6-year-old children. They found that parents' explicit attitudes were not related to children's responses. In contrast, mothers' implicit attitudes (but not fathers' implicit attitudes) were significant predictors of children's attitudes. Results demonstrate that early racial attitudes might develop within the family.

Implicit ingroup metafavoritism: subtle preference for ingroup members displaying ingroup bias.

The current article investigated how individuals evaluate ingroup members displaying either ingroup bias or egalitarian intergroup behaviors. The hypotheses predicted that on explicit responses a preference for the egalitarian ingroup member would emerge; in contrast, on more spontaneous and uncontrolled responses, a preference for the ingroup favoritist would result. Across four studies these hypotheses were confirmed for both minimal groups (Studies 1 and 2) and ethnic groups (Studies 3 and 4). Despite a verbal preference for those who behaved in an egalitarian way, an implicit ingroup metafavoritism was found. Overall, results indicated the presence of dual attitudes in the perception of ingroup members and the strict interconnection between intergroup behaviors and intragroup perception.

Seeing is not stereotyping: the functional independence of categorization and stereotype activation.

Social categorization has been viewed as necessarily resulting in stereotyping, yet extant research suggests the two processes are differentially sensitive to task manipulations. Here, we simultaneously test the degree to which race perception and stereotyping are conditionally automatic. Participants performed a sequential priming task while either explicitly attending to the race of face primes or directing attention away from their semantic nature. We find a dissociation between the perceptual encoding of race and subsequent activation of associated stereotypes, with race perception occurring in both task conditions, but implicit stereotyping occurring only when attention is directed to the race of the face primes. These results support a clear conceptual distinction between categorization and stereotyping and show that the encoding of racial category need not result in stereotype activation.

1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists.

A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with overall favorable developability characteristics were selected for further late lead optimization studies.

Look out for strangers! Sustained neural activity during visual working memory maintenance of other-race faces is modulated by implicit racial prejudice.

We tested the ability of white participants to encode and retain over a brief period of time information about the identity of white and black people, using faces as stimuli in a standard change detection task and tracking neural activity using electroencephalography. Neural responses recorded over the posterior parietal cortex reflecting visual working memory activity increased in amplitude as a function of the number of faces that had to be maintained in memory. Critically, these memory-related neural responses varied as a function of participants' implicit racial prejudice toward black people. High-prejudiced participants encoded black people faces with a lower degree of precision compared to low-prejudiced participants, suggesting that the class of mental operations affected by implicit racial prejudice includes basic cognitive mechanisms underpinning the encoding and maintenance of faces' visual representations in visual working memory.