Silicon-bridged (1→1)-disaccharides: an umpoled glycomimetic scaffold.

Modification of the carbohydrate scaffold is an important theme in drug and vaccine discovery. Therefore, the preparation of novel types of glycomimetics is of interest in synthetic carbohydrate chemistry. In this manuscript, we present an early investigation of the synthesis, structure, and conformational behaviour of (1→1)-Si-disaccharides as a novel type of glycomimetics arising from the replacement of interglycosidic oxygen with a dimethyl-, methylpropyl-, or diisopropylsilyl linkage. We accomplished the preparation of this unusual group of umpoled compounds by the reaction of lithiated glycal or 2-oxyglycal units with dialkyldichlorosilanes. We demonstrated the good stability of the "Si-glycosidic" linkage under acidic conditions even at elevated temperatures. Next, we described the conformational landscape of these compounds by the combination of in silico modelling with spectroscopic and crystallographic methods. Finally, we explained the observed conformational flexibility of these compounds by the absence of gauche stabilizing effects that are typically at play in natural carbohydrates.

Development of Prolinol Containing Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: Rational Structure-Based Drug Design.

Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA and RNA synthesis, resulting in a reduction in cell growth. Therefore, inhibitors of this enzyme have potential to control infections, caused by Plasmodium falciparum and Plasmodium vivax, Trypanosoma brucei, Mycobacterium tuberculosis, and Helicobacter pylori. Five compounds synthesized here that contain a purine base covalently linked by a prolinol group to one or two phosphonate groups have Ki values ranging from 3 nM to >10 µM, depending on the structure of the inhibitor and the biological origin of the enzyme. X-ray crystal structures show that, on binding, these prolinol-containing inhibitors stimulated the movement of active site loops in the enzyme. Against TBr in cell culture, a prodrug exhibited an EC50 of 10 µM. Thus, these compounds are excellent candidates for further development as drug leads against infectious diseases as well as being potential anticancer agents.

Straightforward synthesis of protected 2-hydroxyglycals by chlorination-dehydrochlorination of carbohydrate hemiacetals.

A straightforward and scalable method for the synthesis of protected 2-hydroxyglycals is described. The approach is based on the chlorination of carbohydrate-derived hemiacetals, followed by an elimination reaction to establish the glycal moiety. 1,2-dehydrochlorination reactions were studied on a range of glycosyl chlorides to provide suitable reaction conditions for this transformation. Benzyl ether, isopropylidene and benzylidene protecting groups, as well as interglycosidic linkage, were found to be compatible with this protocol. The described method is operationally simple and allows for the quick preparation of 2-hydroxyglycals with other than ester protecting groups, providing a feasible alternative to existing methods.

Identification and classification of DICOM files with burned-in text content.

BACKGROUND: Protected health information burned in pixel data is not indicated for various reasons in DICOM. It complicates the secondary use of such data. In recent years, there have been several attempts to anonymize or de-identify DICOM files. Existing approaches have different constraints. No completely reliable solution exists. Especially for large datasets, it is necessary to quickly analyse and identify files potentially violating privacy. METHODS: Classification is based on adaptive-iterative algorithm designed to identify one of three classes. There are several image transformations, optical character recognition, and filters; then a local decision is made. A confirmed local decision is the final one. The classifier was trained on a dataset composed of 15,334 images of various modalities. RESULTS: The false positive rates are in all cases below 4.00%, and 1.81% in the mission-critical problem of detecting protected health information. The classifier's weighted average recall was 94.85%, the weighted average inverse recall was 97.42% and Cohen's Kappa coefficient was 0.920. CONCLUSION: The proposed novel approach for classification of burned-in text is highly configurable and able to analyse images from different modalities with a noisy background. The solution was validated and is intended to identify DICOM files that need to have restricted access or be thoroughly de-identified due to privacy issues. Unlike with existing tools, the recognised text, including its coordinates, can be further used for de-identification.