Carbohydrate Mimics and Lectins : A Source of New Drugs and Therapeutic Opportunities

Mimics of oligosaccharides capable of interfering with lectin activity are currently being pursued by a number of groups in an effort to produce tools for glycobiology and to design antagonists of medically relevant lectins. The field is reviewed in this chapter. After a brief overview of the state of the art, examples from our and others' studies on the dendritic cell receptor DC-SIGN are illustrated

2-Azidoethoxy derivatives of 2-aminocyclohexanecarboxylic acids (ACHC): interesting building blocks for the synthesis of cyclic \uf062-peptide conjugates

Oligomers of cyclic beta-aminoacids possess a high resistance to peptidase-catalyzed hydrolysis and display a high intrinsic tendency to adopt regular secondary structures. These characteristics are attractive to develop new biologically active substances. However, cyclic-betapeptides often show limited solubility in water and cannot be conjugated to biologically relevant fragments, such as oligosaccharides, which are often essential for full biololgical activity of natural alfapeptides. In this article, we report the synthesis of one trans- and one cis-2-aminocyclohexane carboxylic acid (ACHC) both functionalized with a hydroxy group, to increase the solubility in water, and an azidoethoxy group to allow the synthesis of cyclic-beta-peptide conjugates by a "click reaction

Effective targeting of DC-sign by α-fucosylamide functionalized gold nanoparticles

Dendritic Cells (DCs), the most potent antigenpresenting cells, play a critical role in the detection of invading pathogens, which are recognized also by multiple carbohydrate-specific receptors. Among them, DC-SIGN is one of the best characterized, with high-mannose and Lewis-type glycan specificity. In this study, we present a potent DC-SIGN targeting device developed using gold nanoparticles functionalized with \u3b1-fucosyl-\u3b2-alanyl amide. The nanoparticles bound to cellular DC-SIGN and induced internalization as effectively as similar particles coated with comparable amounts of LewisX oligosaccharide. They were found to be neutral toward dendritic cell maturation and IL-10 production, thus envisaging a possible use as targeted imaging tools and antigen delivery devices

The mur neutralisant as an active thermal system: Saint Gobain tests (1931) versus CFD simulation (2015)

[EN] At the same time as the initial development of air conditioning systems for indoor climate control in buildings were occurring in USA, Le Corbusier and Lyon made truly innovative proposals for different projects he was working on in Europe. These served to generate homogenous thermal environments and focused on the combined effect of his mur neutralisant and respiration exacte. The clearest example of their shortcomings is the City of Refuge in Paris (1930-33). Given the technological and economic mistrust towards these proposals, as it was impossible to execute these according to the original plan these were not pursued. CFD simulations carried out by our research team confirm that the mur neutralisant and respiration exacte for the City of Refuge in Paris would have functioned together if they had been executed following the original plans. The main aim of this paper is to confirm the validity of the mur neutralisant as an active thermal system for buildings. Firstly, the results of the tests carried out by the engineers of Saint Gobain are compared to the results of the CFD simulations. Based on the comparison of the results from the physical models tested in Saint Gobain laboratories and CFD energy model simulations, a possible calibration is proposed for CFD which might prompt the establishment of other operation hypotheses.Ramírez-Balas, C.; Sendra, J.; Suárez, R.; Fernández-Nieto, E.; Narbona-Reina, G. (2016). The mur neutralisant as an active thermal system: Saint Gobain tests (1931) versus CFD simulation (2015). En LE CORBUSIER. 50 AÑOS DESPUÉS. Editorial Universitat Politècnica de València. 1798-1819. https://doi.org/10.4995/LC2015.2015.899OCS1798181

Comprehensive analysis of blood group antigen binding to classical and El Tor cholera toxin B-pentamers by NMR

Cholera is a diarrheal disease responsible for the deaths of thousands, possibly even hundreds of thousands of people every year, and its impact is predicted to further increase with climate change. It has been known for decades that blood group O individuals suffer more severe symptoms of cholera compared with individuals with other blood groups (A, B and AB). The observed blood group dependence is likely to be caused by the major virulence factor of Vibrio cholerae, the cholera toxin (CT). Here, we investigate the binding of ABH blood group determinants to both classical and El Tor CTB-pentamers using saturation transfer difference NMR and show that all three blood group determinants bind to both toxin variants. Although the details of the interactions differ, we see no large differences between the two toxin genotypes and observe very similar binding constants. We also show that the blood group determinants bind to a site distinct from that of the primary receptor, GM1. Transferred NOESY data confirm that the conformations of the blood group determinants in complex with both toxin variants are similar to those of reported X-ray and solution structures. Taken together, this detailed analysis provides a framework for the interpretation of the epidemiological data linking the severity of cholera infection and an individual's blood group, and brings us one step closer to understanding the molecular basis of cholera blood group dependence

SEOM clinical guideline for the diagnosis and treatment of gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA) (2019)

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, it represents the sixth cause of cancer death. In Western countries, the incidence is decreasing slightly, with an increase in gastroesophageal junction adenocarcinoma (GEJA), a different entity that we separate specifically in the guideline. Molecular biology advances have been done recently, but do not yet lead to the choice in treatment approach except in advanced disease with overexpression of HER2. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors and preliminary immune therapy resulting in advanced disease are the main treatment innovations in the GC/GEJA treatment. We describe the different evidences and recommendations following the statements of the American College of Physicians

The combined use of cross-section analysis and other stratigraphic recording systems in the cleaning of two panel paintings from the fifteenth- and sixteenth-century

Cross sections are frequently used in the stratigraphic study of pictorial structures. Thanks to cross sections, it is possible to study and record original and non-original strata that may provide important information regarding the artist's technique and later restoration processes. This information helps conservators design different strategies in processes such as cleaning. However, it is often in cleaning where the advantages and limitations of cross sections become obvious. When dealing with a complex structure, cross sections may not be enough to record in a comprehensive and accurate manner all the strata removed during cleaning. In some cases, the conservator may obtain during cleaning a great amount of stratigraphic information that is not visible in the cross sections. Therefore, it may be necessary to resort to other recording systems, such as the stratigraphic unit recording sheet and the stratigraphic diagram, which are frequently used in archaeological stratigraphy. This article demonstrates how cross-section analysis was combined with stratigraphic study during the cleaning of two panel paintings to gain an improved understanding of their complicated layer structure.Barros García, JM.; Reina De La Torre, A.; Pérez Marín, E. (2014). The combined use of cross-section analysis and other stratigraphic recording systems in the cleaning of two panel paintings from the fifteenth- and sixteenth-century. Studies in Conservation. 60(4):245-252. doi:10.1179/2047058414Y.0000000128S24525260

Second generation of Fucose-based DC-SIGN ligands : affinity improvement and specificity versus Langerin

DC-SIGN and Langerin are two C-type lectins involved in the initial steps of HIV infections: the former acts as a viral attachment factor and facilitates viral invasion of the immune system, the latter has a protective effect. Potential antiviral compounds targeted against DC-SIGN were synthesized using a common fucosylamide anchor. Their DC-SIGN affinity was tested by SPR and found to be similar to that of the natural ligand Lewis-X (Le X). The compounds were also found to be selective for DC-SIGN and to interact only weakly with Langerin. These molecules are potentially useful therapeutic tools against sexually transmitted HIV infection