1,721,039 research outputs found

    Chemical contributions to understanding heparin activity: Synthesis of related sulfated oligosaccharides

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    Heparin and heparan sulfate are complex polysaccharides that modulate several biological events through the recognition of a number of distinct proteins. Chemical synthesis is a powerful tool to identify the unique binding domains responsible for the specific interactions and to generate potent analogues of the natural sequences. The present review reports the synthetic efforts of the last decade that are focused on the preparation of tailored fragments of these two polymers and analogues thereof. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003

    Ionic liquid mediated synthesis of peptide nucleic acids dimers

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    The unprecedented use of ionic liquids in the synthesis of peptide nucleic acids (PNA) oligomers has been investigated. As a proof of concept, the preparation of PNA dimers in ILs has been performed using last generation coupling reagents. More importantly, the application of the supported ionic liquid phase (SILP) technique to the preparation of a PNA dimer has been achieved, including loading, chain elongation and cleavage from the IL support of the PNA fragment

    Carbohydrates and Immunology : Synthetic Oligosaccharide Antigens for Vaccine Formulation

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    Despite the enormous progress achieved by modern medicine, numerous diseases still have a profound impact on public health. Infectious diseases caused by a variety of microorganisms (viruses, fungi and parasites) and bacteria are a global major concern and, because of the emergence, for instance, of multidrug resistance, not only in developing countries. The development of preventative therapies, such as the rational design of novel and more efficient vaccines, might offer a solution to this state of affairs and other associated drawbacks. Vaccination is considered by the World Health Organization to be the most cost-effective strategy for controlling infectious disease, because it should confer long-term protective immunity in the population. A second consideration involves cancer. The outstanding progress achieved in the identification and structural characterization of tumourassociated antigens has prompted their employment in tumour immunotherapy, on the basis of the observation that tumour cells possess specific antigens that can be recognized by an immune system appropriately conditioned to the task. Carbohydrates play key roles in many molecular recognition phenomena and they can affect any kind of interaction with the immune system. Saccharide-based antigens (bacterial capsular polysaccharides or tumour-associated carbohydrate antigens, for instance) have therefore been studied and employed in the formulation of vaccines. In recent years there has been increasing use of synthetic saccharide antigens for the formulation of vaccine candidates. These structures are indeed chemically well defined, devoid of biologic contaminants and, in principle, available in large amounts, relative to materials extracted from natural sources. In addition, synthetic saccharide antigens can also serve as haptens in protein conjugates, eliciting highly specific antibodies in animal models and humans. The great potential of synthetic saccharide antigens is attested to by the spectacular success of the Cuban vaccine against Haemophilus influenzae type b. Here we review the major advances in the development of synthetic carbohydrate-based vaccines targeted against infectious diseases and cancer

    Synthesis of Fragment of beta-Glucans as Potential Ligands for Dectin-1

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    Beta-glucans are glucose polymers linked together by a 1,3 linear beta-glycosidic chain core, differing from each other by their length and branching configuration. The branches derived from the glycosidic chain core are either 1,4 or 1,6 glycosidic chains and appear to be dependent on the source. Dectin-1 is a unique C-type lectin that recognizes beta-glucan carbohydrates present on the surface of various fungi, including C. albicans. Its activation promotes microbial uptake and phagocytosis, but also mediates, in synergy with TLRs, the production of cytokines such as IL-12 and TNF alfa, leading ultimately to the initiation of the adaptive immune response. For this reason, beta-glucans – or their fragments – can be referred to as a possible class of adjuvants to increase the immune response to pathogens. In addition, the administration of beta-glucan-derived compounds can help in gaining new insights on the mechanism of action of dectin-1 receptor. Dectin-1 binds beta-glucan polymers with affinities ranging from very low (3x10-3 M) to very high (2x10-12 M). The wide range of affinities appears to be due to the differing sizes and numbers of branches in -glucans from various sources. Although the interaction between Dectin-1 and beta-glucans has been supposed to involve a conformational epitope as a high order local helix, little is known about the binding mode and the degree of (1-6)-branching of the glucan chain in the binding epitope. For this reason, a series of fragments of beta-glucans, differing in the 6-O branching degree, has been synthesised. Their ability to bind to dectin-1 and of activating the inflammatory response will be subsequently tested

    Synthesis of PNA in non conventional media

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    The growing awareness of the urgent need for greener, more sustainable technologies has focused the scientific attention on the use of alternative reaction media that circumvent the problems associated with the traditional volatile organic solvents (VOCs). The use of non conventional reaction media also provides opportunities to facilitate the recovery and the recycling of the reaction solvent. Among the most promising alternatives to classical organic solvents, ionic liquids (ILs) have been intensely studied in the recent years as potential environmentally benign reaction media due to their lack of measurable vapour pressure and high thermal and chemical stability. Recently, room temperature Ionic liquids (RTILs) have been used as solvents in the preparation of several classes of biomolecules such as oligosaccharides and peptides. In this communication we report a preliminary study on the use of ILs as solvents in the preparation of peptide nucleic acids (PNAs). The optimization of the reaction conditions, as well as the recycling of the ILs and the use of microwave will be discussed

    Riflessioni per una corretta cultura del debito famigliare

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    Da diversi anni in Italia si è rafforzato il comparto dei finanziamenti rivolti alle famiglie, con riguardo sia al finanziamento dell’investimento immobiliare sia con riguardo al sostegno del consumo. Per alcuni questo elemento è da considerare positivamente, come segnale di sviluppo e ammodernamento del mercato finanziario; per altri ha un prevalente connotato negativo, come segnale di indebolimento delle condizioni finanziarie e della capacità di risparmio dei mutuatari o come una prevalente e diffusa mancanza di consapevolezza e attenzione verso un attento comportamento di spesa. La situazione che si è definita viene puoi giudicata estremamente pericolosa in relazione alle possibili conseguenze di comportamenti superficiali di indebitamento in un contesto di instabilità finanziaria. Le nuove vie di un’attività customer oriented suggeriscono una speranza

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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
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