1,721,033 research outputs found
Synthesis of mono and multivalent pseudosacharide based DC-SIGN ligands : research update
No full textHIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this work, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is described as a promising therapeutic target. The project is being developed within the European research Network CARMUSYS (http://www.carmusys.iiq.csic.es). Herein we show the synthesis of a small library of derivatives of a dimannoside mimic recently reported by our laboratory.1 The mimic was functionalized with two identical amide groups. Further, multivalent presentations of the prepared DC-SIGN ligands were obtained via click chemistry using dendrimeric scaffolds.
The activities of the prepared molecules towards DC-SIGN were determined using surface plasmon resonance (SPR) technique. Multivalency showed significant improvement of the DC-SIGN inhibition in comparison with the corresponding monovalent ligands
Synthesis of inhibitors of DC-SIGN mediated infections
No full textMannose based compounds were synthetised in order to find ligands for DC-SIGN. Pseudo dimmanose based amide synthesis was shown and discoused
STRUCTURAL OPTIMIZATION OF MONO AND MULTIVALENT GLYCOMIMETIC MANNOSE BASED DC-SIGN LIGANDS
Full text linkHIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this work, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is described as a promising therapeutic target. The project is being developed within the European research Network CARMUSYS (http://www.carmusys.iiq.csic.es). Herein we show a synthetic work focused on modifications of a dimannoside mimic previously reported by our laboratory. In the first approach the esters are replaced with two identical amide groups and a small focused library of compounds was prepared. In the second modification, the hydroxyl group in position 6 of the mannose residue is replaced with different substitiuents (i.e. by an amine group.) resulting in a small library of glycomimetics.
The activities of the prepared molecules towards both DC-SIGN and Langherin were determined using surface plasmon resonance (SPR) technique. It was found that the majority of prepared ligands and are better and more selective DC-SIGN inhibitors then the parent molecule.
Further, synthesis of rigid, water soluble spacers – molecular rods is described which were connected to dendrimeric scaffolds bearing the prepared monovalent ligands mentioned above
The prepared multivalent structures were tested by SPR technique. Multivalency showed significant improvement of the DC-SIGN inhibition in comparison with the corresponding monovalent ligands
Multivalent DC-SIGN ligands with a rigid core of controlled lenght
No full textHuman immunodeficiency virus (HIV) is still a huge health problem of the 21st century, causing the death of over 1 million people per year. The search for HIV-entry inhibitors represents a promising challenge to prevent HIV infection. In this field, dendritic cell-specific ICAM-3 grabbing non-integrine (DC-SIGN), expressed at the surface of the mucosal dendritic cells (DC) and involved in the early stages of HIV infection, is an important cellular target.1
DC-SIGN is a calcium-dependant tetrameric lectin; it recognizes high-mannose oligosaccharides displayed at the surface of HIV virus and interacts with them through strong multiple interactions. Therefore, artificial molecules displaying multivalent carbohydrate moieties, able to interact with DC-SIGN with good affinity, should prevent HIV attachment to DC and therefore HIV infection.
In our group, several DC-SIGN mannose-based ligands have been prepared and tested as HIV inhibitors; glycomimetic compounds were used rather than native oligosaccharides.2, 3
Here we present a library of multivalent glycomimetic compounds potentially able to bind simultaneously two binding sites on DC-SIGN, thus exploiting the chelating binding mode to enhance their affinity for the target. Compounds were synthesised by varying the length of a rigid aromatic scaffold and the nature as well as the valency of the sugar moieties at each end of the central core.
Some of the synthesised compounds were tested for the ability to inhibit HIV transmission in an in vitro trans infection assay, revealing a high activity that seems depend on scaffold length. Tests were performed by Dr. Angela Berzi in the laboratories of Prof. Mario Clerici (University of Milan).
Synthetic pathways and tests results will be presented
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
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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