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Modulation of Antithrombin-Protease Interactions by Semisynthetic Low-Molecular-Weight Heparins with Different Sulfation Patterns
No full textHeparin, a natural glycosaminoglycan (GAG), is widely used for the treatment of thrombotic diseases. Most of its side effects are related to its ability to bind to different proteins, thus interfering with their target biological activity. To gain insight into structure-activity relationships, we investigated the interaction of an homogeneous series of sulfated polysaccarides, deriving from controlled desulfation of a supersulfated low molecular weight heparin (LMWH) with the target-enzymes human Antithrombin III (AT) and thrombin (T). In addition, we analyzed the activation process of the serpin AT against T and Factor Xa (Xa). A non-linear correlation between the strength of the AT-heparin complex and the polysaccharide sulfation degree was observed, whereas only a modest modulation of T binding to heparin occurred. The efficiency of the LMWH derivatives in activating AT towards the proteases was generally high for derivatives exhibiting a low dissociation constant. Only the supersulfated heparin showed a serpin activation ability higher than expected from the affinity studies.
Examination of the sulfation pattern in the light of the above results suggests a key role of the substitution of the iduronic acid residue in the heparin-mediated serpin binding and activation processes. Indeed, sulfation at position 2 of the uronic acid is beneficial, whereas 2,3-disubstitution generates unfavorable contacts between the GAG and AT. On turn, glucosamine sulfation at position 6 appears to grant increased catalytic efficiency.
These results indicate that chemical modification of heparin sulfation pattern can be used to modulate binding specificity and activity towards its biological targets
MIMETICS OF SULFATED OLIGOSACCHARIDES
No full textThe present invention is directed to sulfated oligosaccharides having 4, 5 or 6 saccharidic units and wherein a glycosidic bond between two saccharide units is substituted by a C-C bond, and wherein the sulfation degree expressed as percentage of OH groups substituted by a OSO 3 - group is comprised between 50 and 100 %. The sulfated oligosaccharides according to the invention are useful as a drug, in particular in the treatment of angiogenesis, metastasis, and inflammation
SYNTHETIC GLYCOSAMINOGLYCAN PENTASACCHARIDES FOR INHIBITION OF ENZIMATIC ACTIVITY OF HEPARANASE
No full textHeparanase is an enzyme that is over-expressed in spme pathological conditions such as tumor growth, metastasis and heavy inflammation forms.Therefore the development of inhibitors of HSase activity is an important target for designing antiangiogenic and antimetastatic agents.
In this work there were studied and tested three different oligosaccharides using a method based on direct quantification of residual substrate by mass spectroscopy (ESI.IT) coupled with chromatographic separation (HPLC)
Structure and conformation of polyalcohols and polyacids obtained from periodate oxyamylose and oxycellulose
No full textGoing 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
"Reactivity of carbohydrate radicals derived from iodo sugars and dibenzoyl peroxide: Homolytic heteroaromatic and aromatic substitution, reduction and oxidation."
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