1,720,994 research outputs found
Amine Exchange and Unexpected Ring Opening Reaction on Pyranone Derivatives : Synthesis of 3-Amino-Substituted Oxonaphthopyrancarbaldehydes and Tetrahydropyrimidinethanones as New Potential Oligonucleotide Stabilization Agents
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Influence of the Nitrogen Substitution in Three Cytisine Derivatives as Ligands for the Neuronal nAChRs: A Structural and Theoretical Study
No full textThree cytisine derivatives, ()-(7R,9S)-1-phenyl-3-(cytisin-12-yl)propan-1-one (1), ()-(7R,9S)-1-
phenyl-2-(cytisin-12-yl)ethane (2), and ()-(7R,9S)-1,2-bis(cytisin-12-yl)ethane (3), with different
electronic and steric features have been characterized by X-ray analysis and theoretical calculations in
order to evaluate how structural modulations affect the intrinsic binding affinity at the neuronal nicotinic
receptors (nAChRs). The crystal structures of 1 and 2, which display comparable affinities, are
characterized by the same conformation of the cytisine moiety with different orientations of the
substituent at N(2). In 3, two independent molecules have the pyridinone rings diversely oriented. This
compound has a lower affinity with respect to 1 and 2, but it increases the expression of neuronal
nAChRs. Compounds 1, 2, and 3 retain the key prerequisite of the classical pharmacophoric models, with
sp3-N-atomHBA distances close to the expected value, both in solid state and in solution (theoretical
calculations), where, in contrast with the extended in the crystal state, a curled-up conformation has been
found, though maintaining the N-substituent in equatorial position
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Novel Functionalized Pyridine-Containing DTPA-like Ligand. Synthesis, Computational Studies and Characterization of the Corresponding Gd(III) Complexes
No full textInteractions between atypical opioid agonists and MOR
No full textEndomorphins (EMs) are endogenous peptides with high selectivity for MOR; they induce strong antinociception by binding to both central and peripheral MOR but, unlike morphine, they are effective in reducing neuropathic pain and their analgesic effect seems to be dissociated by immunomodulatory, cardiovascular and respiratory effects. As native EMs show poor bioavailability and rapid degradation in vivo, we designed and assayed novel EM-1 (YPWF-NH2) derivatives bearing chemical modification aimed to improve their application as analgesics. The ionic bond between a protonated amine and a conserved Asp in the third TMH of the opioid receptor is considered the driving force for ligand-receptor interaction of all opioid agonists, being the amine of Tyr the key pharmacophore for opioid peptides. The removal or derivatization of this pharmacophore usually transforms agonists into inactive compounds or antagonists, with only few compounds maintaining an agonist behaviour when deprived of such amino group. Recently, we discovered the novel EM-1 derivative c[YpwFG]; it displayed good affinity to MOR (Ki 34 nM), is an effective and potent analgesic for visceral pain when administered peripherally (i.p ED50 1,25 mg/kg; s.c. ED50 2,7 mg/kg), and retains central analgesic effects (tail-flick test) only at high doses (20 mg/kg). Interestingly, it triggers MOR internalization similarly to DAMGO but displayed an opposite effect on MOR transcription. This cyclopeptide is a structurally atypical opioid agonist, being deprived of the key pharmacophore, therefore we performed investigations by 2D-NMR, conformational analysis, and molecular docking to provide insights into its interaction with and activation of MOR. The resulting receptor-bound structure served as a general model to design new MOR-active compounds containing the sequence wF, to optimize ligand-receptor interactions. This search lead to c[YGwFG], which showed a 10- fold higher affinity for the MOR (Ki 3,6 nM) as well as good analgesic properties in vivo. Finally, we verified the predictive power of the general model by designing a non-EM-like opioid compound, the cyclic tetrapeptide c[d(1-NH2)beta-AwF]. In summary, these results suggest that alternative interactions might duly replace the electrostatic interaction of the protonated nitrogen with the Asp residue, which has not to be considered a conditio sine qua non for opioid receptor activatio
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