ABSTRACT
Group A Carbohydrate (GAC), conjugated to an appropriate carrier protein, has been proposed as an attractive vaccine candidate against Group A Streptococcus infections. Native GAC consists of a polyrhamnose (polyRha) backbone with N-acetylglucosamine (GlcNAc) at every second rhamnose residue. Both native GAC and the polyRha backbone have been proposed as vaccine components. Here, chemical synthesis and glycoengineering were used to generate a panel of different length GAC and polyrhamnose fragments. Biochemical analyses were performed confirming that the epitope motif of GAC is composed of GlcNAc in the context of the polyrhamnose backbone. Conjugates from GAC isolated and purified from a bacterial strain and polyRha genetically expressed in E. coli and with similar molecular size to GAC were compared in different animal models. The GAC conjugate elicited higher anti-GAC IgG levels with stronger binding capacity to Group A Streptococcus strains than the polyRha one, both in mice and in rabbits. This work contributes to the development of a vaccine against Group A Streptococcus suggesting GAC as preferable saccharide antigen to include in the vaccine.
Subject(s)
Acetylglucosamine , Vaccines , Mice , Animals , Rabbits , Acetylglucosamine/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Carbohydrates , Streptococcus pyogenes/metabolism , Glycoconjugates/metabolismABSTRACT
In this work a photosubstitution strategy is presented that can be used for the isolation of chiral organometallic complexes. A series of five cyclometalated complexes Ru(phbpy)(N-N)(DMSO-κS)](PF6) ([1]PF6-[5]PF6) were synthesized and characterized, where Hphbpy = 6'-phenyl-2,2'-bipyridyl, and N-N = bpy (2,2'-bipyridine), phen (1,10-phenanthroline), dpq (pyrazino[2,3- f][1,10]phenanthroline), dppz (dipyrido[3,2- a:2',3'- c]phenazine, or dppn (benzo[ i]dipyrido[3,2- a,2',3'- c]phenazine), respectively. Due to the asymmetry of the cyclometalated phbpy- ligand, the corresponding [Ru(phbpy)(N-N)(DMSO-κS)]+complexes are chiral. The exceptional thermal inertness of the Ru-S bond made chiral resolution of these complexes by thermal ligand exchange impossible. However, photosubstitution by visible light irradiation in acetonitrile was possible for three of the five complexes ([1]PF6-[3]PF6). Further thermal coordination of the chiral sulfoxide ( R)-methyl p-tolylsulfoxide to the photoproduct [Ru(phbpy)(phen)(NCMe)]PF6, followed by reverse phase HPLC, led to the separation and characterization of the two diastereoisomers of [Ru(phbpy)(phen)(MeSO(C7H7))]PF6, thus providing a new photochemical approach toward the synthesis of chiral cyclometalated ruthenium(II) complexes. Full photochemical, electrochemical, and frontier orbital characterization of the cyclometalated complexes [1]PF6-[5]PF6 was performed to explain why [4]PF6 and [5]PF6 are photochemically inert while [1]PF6-[3]PF6 perform selective photosubstitution.
ABSTRACT
A new, fast, mild and chemoselective deprotection method to cleave p-methoxybenzyl and 2-naphthylmethyl ethers using catalytic amounts of hydrochloric acid in a 1:1 mixture of hexafluoro-2-propanol (HFIP) and methylene chloride (DCM) is described. The scope of the methodology becomes apparent from 14 examples of orthogonally protected monosaccharides that are subjected to HCl/HFIP treatment. The applicability of the HCl/HFIP method is illustrated by the synthesis of a sulfated ß-mannuronic acid disaccharide.
ABSTRACT
Well-defined fragments of hyaluronic acid (HA) have been obtained through a fully automated solid-phase oligosaccharide synthesis. Disaccharide building blocks, featuring a disarmed glucuronic acid donor moiety and a di-tert-butylsilylidene-protected glucosamine part, were used in the rapid and efficient assembly of HA fragments up to the pentadecamer level, equipped with a conjugation-ready anomeric allyl function.
