Initial properdin binding contributes to alternative pathway activation at the surface of viable and necrotic cells

Properdin, the only known positive regulator of the complement system, stabilizes the C3 convertase, thereby increasing its half-life. In contrast to most other complement factors, properdin is mainly produced extrahepatically by myeloid cells. Recent data suggest a role for properdin as a pattern recognition molecule. Here, we confirmed previous findings of properdin binding to different necrotic cells including Jurkat T cells. Binding can occur independent of C3, as demonstrated by HAP-1 C3 KO cells, excluding a role for endogenous C3. In view of the cellular source of properdin, interaction with myeloid cells was examined. Properdin bound to the surface of viable monocyte-derived pro- and anti-inflammatory macrophages, but not to DCs. Binding was demonstrated for purified properdin as well as fractionated P2, P3, and P4 properdin oligomers. Binding contributed to local complement activation as determined by C3 and C5b-9 deposition on the cell surfaces and seems a prerequisite for alternative pathway activation. Interaction of properdin with cell surfaces could be inhibited with the tick protein Salp20 and by different polysaccharides, depending on sulfation and chain length. These data identify properdin as a factor interacting with different cell surfaces, being either dead or alive, contributing to the local stimulation of complement activation.</p

NIS/TFA: a general method for hydrolyzing thioglycosides

A variety of thioglycosides are chemoselectively hydrolyzed to the corresponding 1-hydroxy glycosides using equimolar amounts of NIS/TFA as promoter systems.

C-Terminal Peptide Modification: Merging the Passerini Reaction with Chemo-Enzymatic Synthesis

Over the past few decades, peptide/protein synthesis and bio-conjugation has gained increasing interest in the research community owing to the high demand for strategies that provide modified protein adducts in a site-selective fashion. Herein, we report a novel approach that combines the Passerini multicomponent reaction and chemo-enzymatic peptide synthesis (CEPS) for the selective bio-conjugation of peptide C-termini. The Passerini utilizes aqueous acidic buffer conditions to establish chemoselectivity for the carboxylic acids, while the subsequent enzymatic ligation selectively targets the formed C-terminal substrates. We functionalized a diverse set of pentapeptides utilizing numerous isocyanide and car-bonyl compounds and successfully performed subsequent ligations. This combined multicomponent chemoenzymatic method therefore represents a valuable novel technology for future research into site-selective C-terminal modification of peptides/proteins

The impact of oxacarbenium ion conformers on the stereochemical outcome of glycosylations

The search for stereoselective glycosylation reactions has occupied synthetic carbohydrate chemists for decades. Traditionally, most attention has been focused on controlling the S(N)2-like substitution of anomeric leaving groups as highlighted by Lemieux's in situ anomerization protocol and by the discovery of anomeric triflates as reactive intermediates in the stereoselective formation of beta-mannosides. Recently, it has become clear that also S(N)1-like reaction pathways can lead to highly selective glycosylation reactions. This review describes some recent examples of stereoselective glycosylations in which oxacarbenium ions are believed to be at the basis of the selectivity. Special attention is paid to the stereodirecting effect of substituents on a pyranosyl ring with an emphasis on the role of the C-5 carboxylate ester in the condensations of mannuronate ester donors. (C) 2010 Elsevier Ltd. All rights reserved