Unveiling the sugary secrets of plasmodium parasites

Plasmodium parasites cause malaria disease, one of the leading global health burdens for humanity, infecting hundreds of millions of people each year. Different glycans on the parasite and the host cell surface play significant roles in both malaria pathogenesis and host defense mechanisms. So far, only small, truncated N- and O-glycans have been identified in Plasmodium species. In contrast, complex glycosylphosphatidylinositol (GPI) glycolipids are highly abundant on the parasite's cell membrane and are essential for its survival. Moreover, the parasites express lectins that bind and exploit the host cell surface glycans for different aspects of the parasite life cycle, such as adherence, invasion, and evasion of the host immune system. In parallel, the host cell glycocalyx and lectin expression serve as the first line of defense against Plasmodium parasites and directly dictate susceptibility to Plasmodium infection. This review provides an overview of the glycobiology involved in Plasmodium-host interactions and its contribution to malaria pathogenesis. Recent findings are presented and evaluated in the context of potential therapeutic exploitation

Multivalent glycan arrays

Glycan microarrays have become a powerful technology to study biological processes, such as cell–cell interaction, inflammation, and infections. Yet, several challenges, especially in multivalent display, remain. In this introductory lecture we discuss the state-of-the-art glycan microarray technology, with emphasis on novel approaches to access collections of pure glycans and their immobilization on surfaces. Future directions to mimic the natural glycan presentation on an array format, as well as in situ generation of combinatorial glycan collections, are discussed

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

Pushing the Limits of Automated Glycan Assembly: Synthesis of a 50mer Polymannoside

Automated glycan assembly (AGA) enables rapid access to oligosaccharides. The overall length of polymers created via automated solid phase synthesis depends on very high yields at every step to obtain full length product. The synthesis of long polymers serves as the ultimate test of the efficiency and reliability of synthetic processes. A series of Man-(1[rightward arrow]6)-[small alpha]-Man linked oligosaccharides up to a 50mer, the longest synthetic sequence yet assembled from monosaccharides, has been realized via a 102 step synthesis. We identified a suitable mannose building block and applied a capping step in the final five AGA cycles to minimize (n-1) deletion sequences that are otherwise difficult to remove by HPLC

Position matters : fluorescent positional isomers for reversible multichannel encryption devices

Fluorescence signals have been widely used in information encryption for a few decades, but still suffer from limited reliability. Here, reversible multichannel fluorescent devices with encrypted information were constructed, based on two fluorescent positional isomers of a diphenylquinoxaline derivative. Possessing the same core fluorescent group and acid-/pH-responsive mechanism, the two isomers showed different fluorescence color in an acidic environment, which allowed us to realize stepwise encryption of information in orthogonal fluorescence channels. Since the protonation was reversible, the revealed information could be re-encrypted, simply by heating. This approach highlights the value of positional isomers to build multichannel encryption devices, improving their reliability on the molecular level

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks. Highly efficient in flow conjugation of thioglycosides to a double-bond presenting diethylentriamine precursor is the key step to prepare these building blocks suitable for fully automated solid-phase synthesis. Introduction of the sugar ligands via functionalized building blocks rather than postfunctionalization of the oligomeric backbone allows for the straightforward synthesis of multivalent glycoligands with full control over monomer sequence and functionalization pattern. We demonstrate the potential of this building-block approach by synthesizing oligomers with different numbers and spacing of carbohydrates and also show the feasibility of heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides

Automated glycan assembly of peptidoglycan backbone fragments

We report the automated glycan assembly (AGA) of different oligosaccharide fragments of the bacterial peptidoglycan (PGN) backbone. Iterative addition on a solid support of an acetyl glucosamine and a new muramic acid building block is followed by cleavage from the solid support and final deprotection providing 10 oligosaccharides up to six units

Bupivacaine concentrations in lumbar cerebrospinal fluid in patients with failed spinal anaesthesia

Background Spinal anaesthesia (SA) has high success rates. However, inadequate block after SA has been reported even in the absence of technical problems. Various mechanisms for failed SA (FSA) have been proposed, but reports of cerebrospinal fluid (CSF) concentrations of local anaesthetics (LA) after FSA are scarce. We report lumbar CSF concentrations of bupivacaine in 20 patients in whom adequate block after subarachnoid injection failed to develop. Methods All patients with inadequate block after subarachnoid injection of plain bupivacaine 0.5% and in whom a second subarachnoid injection of LA was to be performed as a rescue technique were eligible for entry into this study. A CSF sample was withdrawn immediately before injection of the second dose of LA. Patients in whom failure was obviously due to technical problems or inadequate dosage were excluded. Bupivacaine concentrations were assessed with high-performance liquid chromatography. Results During the study period of 15 months, 2600 spinal anaesthetics were performed. The failure rate was 2.7% (71 patients). In 20 patients (0.77%), CSF concentrations of bupivacaine were determined, which ranged from 3.36 to 1020 µg ml−1. Conclusions Inadequate CSF concentration of LA is a common reason for FSA. However, in 12 of our 20 patients, concentrations were above 73 µg ml−1, a concentration that should lead to an adequate block. In these patients, maldistribution of bupivacaine could be responsible for FSA. In view of the absence of sufficient block, despite adequate lumbar CSF concentrations of bupivacaine, concerns about neurotoxicity with repeat injections may be warrante