Gerhard Baschang

Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides

In allergy and asthma, the fine balance between the T helper (Th) 1, Th2 and T regulatory cytokine responses appears to be shifted towards Th2. Here, we report that synthetic lipopeptides which contain the typical lipid part of the lipoprotein of gram‐negative bacteria stimulate a distinct regulatory cytokine pattern and inhibit several Th2 cell‐related phenomena. The most potent analogue of synthetic lipopeptides, lipopeptide CGP 40774 (LP40) was not active in MyD88‐deficient mice and stimulated Toll‐like receptor (TLR)‐2, but not TLR‐4. LP40 potentiated the production of IFN‐γ and IL‐10, but not IL‐4 and IL‐5 by human T cells. In addition, triggering of TLR‐2 by lipopeptides promoted the in vitro differentiation of naive T cells towards IL‐10‐ and IFN‐γ‐producing T cells and suppressed IL‐4 production by Th2 cells. Accordingly, LP40 inhibited IgE production induced by allergen, anti‐IgD antibody, Nippostrongylus brasiliensis or murine acquired immunodeficiency virus. Furthermore, ovalbumin‐induced lung eosinophilic inflammation was abolished and Schistosoma mansoni egg‐induced granuloma size and eosinophil counts were suppressed in mice by LP40. These results demonstrate that stimulation of TLR‐2 by lipopeptides represents a novel way for possible treatment of allergy and asthma by regulating the disrupted cytokine balance.

Synthesis of the HSA-conjugate of the S-linked thiomimetic of the branched tetrasaccharide repeating unit of the immunostimulant polysaccharide, schizophyllan. Evaluation as potential immunomodulator

The conjugate with human serum albumin (HSA) of the S-linked thioanalogue of the branched tetrasaccharide repeating unit of the polysaccharide, schizophyllan, was synthesized from 1,2,4,6-tetra-O-acetyl-3-S-[2,4-di-O-acetyl-3,6-di-S-(2,3,4,6-tetra-O-ac etyl-beta-D-glucopyranosyl)-3,6-dithio-beta-D-glucopyranosyl]-3-thio-bet a-D-glucopyranose [M.O. Contour-Galcera et al., Carbohydr. Res., 281 (1996) 119-128] in five steps, and its potential immunomodulatory activity was evaluated in human blood mononuclear cells. The protein glycoconjugate did not effect proliferation or production of IL-4, IL-5 and IFN-g in a significant way.

The enantiomers of 1β-adenyl-2α-hydroxy-3β-hydroxymethyl-cyclobutane

Abstract The enantiomers of 1β-adenyl-2α-hydroxy-3β-hydroxymethyl-cyclobutane have been separated by chromatography of their 2-(N-BOC-prolyl)-3-trityloxymethyl-derivatives. The (−)-enantiomer has been obtained from 1.2-dihydroxy-3-trityloxymethyl-cyclobutane enriched by acetylation of the racemate with Pseudomonas fluorescens lipase.

Synthesis of an Octameric Phosphodiester of 2, 3-dideoxy-ß-D-erythro-hex-2-eno-pyranosyl-thymine and Its Interactions with Poly-rA and Poly-dA

Abstract 2, 3-Dideoxy-s-D-erythro-hex-2-eno-pyranosyl-thymine 1 was converted to an octanucleotide by the H-phosphonate method. This octamer did not hybridize with poly-rA in 1 M NaCl (pH 7) but did so, to a small extent, with poly-dA. One unsaturated nucleotide was incorporated in the middle of a hepta-thymidylate to probe the disorder caused by this foreign building block.