Acylsulfonamide safety-catch linker : promise and limitations for solid-phase oligosaccharide synthesis

Safety-catch linkers are useful for solid-phase oligosaccharide synthesis as they are orthogonal to many common protective groups. A new acylsulfonamide safety-catch linker was designed, synthesized and employed during glycosylations using an automated carbohydrate synthesizer. The analysis of the cleavage products revealed shortcomings for oligosaccharide synthesis

Automated access to well-defined ionic oligosaccharides

Ionic polysaccharides are part of many biological events, but lack structural characterisation due to challenging purifications and complex synthesis. Four monosaccharides bearing modifications not found in nature are used for the automated synthesis of a collection of ionic oligosaccharides. Structural analysis reveals how the charge pattern affects glycan conformation

Chemical synthesis of phosphatidylinositol mannoside glycans from Mycobacterium tuberculosis

The efficient synthesis of phosphatidylinositol mono- to hexa-mannoside (PIM1 to PIM6) is reported. The invention relates to these phosphatidylinositol mono- to hexa-mannosides carrying a linker and a reactive functional group, e.g. the sulfhydryl group, a protein, a fluorescent probe, or a solid phase. The invention further relates to vaccines comprising the PIMs linked to a carrier protein or an antigen

Remifentanil does not impair left ventricular systolic and diastolic function in young healthy patients

Background Experimental studies and investigations in patients with cardiac diseases suggest that opioids at clinical concentrations have no important direct effect on myocardial relaxation and contractility. In vivo data on the effect of remifentanil on myocardial function in humans are scarce. This study aimed to investigate the effects of remifentanil on left ventricular (LV) function in young healthy humans by transthoracic echocardiography (TTE). We hypothesized that remifentanil does not impair systolic, diastolic LV function, or both. Methods Twelve individuals (aged 18-48 yr) without any history or signs of cardiovascular disease and undergoing minor surgical procedures under general anaesthesia were studied. Echocardiographic examinations were performed in the spontaneously breathing subjects before (baseline) and during administration of remifentanil at a target effect-site concentration of 2 ng ml−1 by target-controlled infusion. Analysis of systolic function focused on fractional area change (FAC). Analysis of diastolic function focused on peak early diastolic velocity of the mitral annulus (e′) and on transmitral peak flow velocity (E). Results Remifentanil infusion at a target concentration of 2 ng ml−1 did not affect heart rate or arterial pressure. There was no evidence of systolic or diastolic dysfunction during remifentanil infusion, as the echocardiographic measure of systolic function (FAC) was similar to baseline, and measures of diastolic function remained unchanged (e′) or improved slightly (E). Conclusion Continuous infusion of remifentanil in a clinically relevant concentration did not affect systolic and diastolic LV function in young healthy subjects during spontaneous breathing as indicated by TT

Remote participation during glycosylation reactions of galactose building blocks: Direct evidence from cryogenic vibrational spectroscopy

The stereoselective formation of 1,2‐cis‐glycosidic bonds is challenging. However, 1,2‐cis‐selectivity can be induced by remote participation of C4 or C6 ester groups. Reactions involving remote participation are believed to proceed via a key ionic intermediate, the glycosyl cation. Although mechanistic pathways were postulated many years ago, the structure of the reaction intermediates remained elusive owing to their short‐lived nature. Herein, we unravel the structure of glycosyl cations involved in remote participation reactions via cryogenic vibrational spectroscopy and first principles theory. Acetyl groups at C4 ensure α‐selective galactosylations by forming a covalent bond to the anomeric carbon in dioxolenium‐type ions. Unexpectedly, also benzyl ether protecting groups can engage in remote participation and promote the stereoselective formation of 1,2‐cis‐glycosidic bonds

Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre-existing diastolic dysfunction

Background. The effects of anaesthetics on left ventricular (LV) diastolic function in patients with pre-existing diastolic dysfunction are not well known. We hypothesized that propofol but not sevoflurane will worsen the pre-existing LV diastolic dysfunction. Methods. Of 24 randomized patients, 23 fulfilled the predefined echocardiographic criterion for diastolic dysfunction. They received general anaesthesia with sevoflurane 1 MAC (n=12) or propofol 4 μg ml−1 (n=11). Echocardiographic examinations were performed at baseline and in anaesthetized patients under spontaneous breathing and under positive pressure ventilation. Analysis focused on peak early diastolic velocity of the mitral annulus (Ea). Results. During spontaneous breathing, Ea was higher in the sevoflurane than in the propofol group [mean (95% CI) 7.0 (5.9-8.1) vs 5.5 (4.7-6.3) cm s−1; P<0.05], reflecting an increase of Ea from baseline only in the sevoflurane group (P<0.01). Haemodynamic findings were similar in both groups, but the end-tidal carbon dioxide content was more elevated in the propofol group (P<0.01). During positive pressure ventilation, Ea was similarly low in the sevoflurane and propofol groups [5.3 (4.2-6.3) and 4.4 (3.6-5.2) cm s−1, respectively]. Conclusions. During spontaneous breathing, early diastolic function improved in the sevoflurane but not in the propofol group. However, during positive pressure ventilation and balanced anaesthesia, there was no evidence of different effects caused by the two anaesthetic

Automated glycan assembly of oligosaccharides related to arabinogalactan proteins

Arabinogalactan proteins are heavily glycosylated proteoglycans in plants. Their glycan portion consists of type-II arabinogalactan polysaccharides whose heterogeneity hampers the assignment of the arabinogalactan protein function. Synthetic chemistry is key to the procurement of molecular probes for plant biologists. Described is the automated glycan assembly of 14 oligosaccharides from four monosaccharide building blocks. These linear and branched glycans represent key structural features of natural type-II arabinogalactans and will serve as tools for arabinogalactan biology