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

Process for the modification of polymers, in particular polymer nanoparticles

The present invention relates to a highly efficient and ultra fast process for the photo-initiated preparation of polymers by polymerization using photoinitiators comprising a phosphorous oxide or -sulfide group and modification of said polymers. In particular the invention relates to an ultra fast process for the photo-initiated preparation of latices comprising polymer nanoparticles by heterophase polymerization using photoinitiators comprising a phosphorous oxide or -sulfide group and their modification. In another aspect, the invention relates to polymers and polymer nanoparticles obtainable by said process

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

A traceless photocleavable linker for the automated glycan assembly of carbohydrates with free reducing ends

We report a traceless photocleavable linker for the automated glycan assembly of carbohydrates with free reducing ends. The reductive-labile functionality in the linker tolerates all commonly used reagents and protocols for automated glycan assembly, as demonstrated with the successful preparation of nine plant cell wall-related oligosaccharides, and is cleaved by hydrogenolysis

Factor H-related protein 1 neutralizes anti-factor H autoantibodies in autoimmune hemolytic uremic syndrome.

The autoimmune form of atypical hemolytic uremic syndrome (HUS) is characterized by circulating autoantibodies against the complement regulator factor H, and is often associated with deficiency of the factor H-related proteins CFHR1 and CFHR3. Here we studied whether anti-factor H autoantibodies crossreact with CFHR1, and determined functional consequences of this. In ELISA, anti-factor H immunoglobulin G (IgG) autoantibodies from 24 atypical HUS patients bound to the short consensus repeat 20 domain of factor H, 21 antibodies also recognized CFHR1, but none CFHR3. Three patients also had anti-factor H IgA autoantibodies crossreacting with CFHR1. Analysis of the IgG fractions in CFHR1-deficient patients found that CFHR1-IgG complexes were formed during plasma exchange treatment, indicating that autoantibodies recognize CFHR1 in vivo. Recombinant CFHR1 prevented hemolysis of sheep erythrocytes caused by patient plasma containing anti-factor H IgG, but it did not inhibit red cell lysis caused by a factor H mutation (W1183 L) in the short consensus repeat 20 domain. Thus, exogenous CFHR1 provided during plasma exchange therapy may neutralize anti-factor H autoantibodies and help in the treatment of autoimmune atypical HUS

Transthoracic echocardiography for perioperative haemodynamic monitoring

Transoesophageal echocardiography (TOE) is valuable for perioperative monitoring in patients at risk from haemodynamic disturbance. However, its use is not practicable in patients undergoing surgical procedures under regional anaesthesia. We describe two cases showing that transthoracic echocardiography (TTE) has the same advantages as TOE and thus may be valuable for monitoring awake patients. TTE should be considered when extended perioperative haemodynamic monitoring is needed but TOE is not possibl

Distinguishing N-acetylneuraminic acid linkage isomers on glycopeptides by ion mobility-mass spectrometry

Differentiating the structure of isobaric glycopeptides represents a major challenge for mass spectrometry-based characterisation techniques. Here we show that the regiochemistry of the most common N-acetylneuraminic acid linkages of N-glycans can be identified in a site-specific manner from individual glycopeptides using ion mobility-mass spectrometry analysis of diagnostic fragment ions