Hamburg, Univ., Diss., 2002. / Computerdatei im Fernzugriff.

Hamburg, Univ., Diss., 2002. / Computerdatei im Fernzugriff.

Hamburg, Universiẗat, Diss., 2004.

Hamburg, Universiẗat, Diss., 2002.

No description available.

According to the traditional paradigm, carbohydrates are considered to be poorly immunogenic, T-cell independent antigens. Pure polysaccharides induce specific IgM responses, with minimal class switch to IgG. However, a series of recent investigations has found that a class of zwitterionic polysaccharides (ZPSs)induces a variety of T-cell specific responses such as cell proliferation,cytokine secretion, and regulation of antibody production. The two most studied among this family of molecules is capsular polysaccharide (PS) A1 from the Bacteroides fragilis and the type 1 Streptococcus pneumoniae polysaccharide capsule (Sp1). Active ZPSs share a common structural motif; a high density of positively charged amino and negatively charged carboxyl or phosphate groups. These features are essential for the activity of ZPSs. Since the biological repeating unit of the polysaccharides is not known and biological activity will most likely depend upon a precise sequence, synthesis of the repeating unit of these capsular polysaccharides was undertaken. The goal of this work is to synthesize the repeating unit [3)--DFucpN2AcN4-( 14)--D-GalpA-(13)--D-GalpA-(1] of the type 1 capsular polysaccharide (Sp1) found in S. pneumoniae. 2-Acetamido-4-amino-2,4,6- trideoxy-D-galactopyranose is one of the three monosaccharides of the repeating unit of the Sp1 of Streptococcus pneumoniae. This rare amino sugar is also present in a number of bacterial polysaccharides such as Bacteroids fragilis, Streptococcus mitis and Shigella sonnei. We have developed a novel method to synthesize the orthogonally protected 2-acetamido-4-amino-2,4,6-trideoxy-Dgalactopyranose on a gram scale with high yield starting from readily available Dglucal. The crucial elements of this approach are the introduction of a 4 amino function via intramolecular cyclization of a 3-O-N-benzylcarbamate. The resulting N-benzyloxazolidinone derivative after conversion to the corresponding glycosyl trichloroacetimidate was shown to be an effective glycosyl donor. The assembly of the trisaccharide was successfully carried out from the appropriate galactopyranosides selectively protected at O-6 to permit oxidation to uronic acid derivatives after successful assembly of the target trisaccharide. The trisaccharide was tested for its ability to stimulate interleukin 10 (IL-10) and Interferon-gamma (IFN-) in collaboration with Dr. Dennis L. Kasper (Channing Laboratory, Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts, USA). Unfortunately the trisaccharide was not active. / Chemistry

Abstract: Drug dosage forms contain many components in addition to the active pharmaceutical ingredient(s) to assist in the manufacturing process as well as to optimise drug delivery. Due to advances in drug delivery technology, excipients are currently included in novel dosage forms to fulfil specific functions and in some cases they directly or indirectly influence the extent and/or rate of drug release and absorption. Since plant polysaccharides comply with many requirements expected of pharmaceutical excipients such as non-toxicity, stability, availability and renewability they are extensively investigated for use in the development of solid oral dosage forms. Furthermore, polysaccharides with varying physicochemical properties can be extracted from plants at relatively low cost and can be chemically modified to suit specific needs. As an example, many polysaccharide-rich plant materials are successfully used as matrix formers in modified release dosage forms. Some natural polysaccharides have even shown environmental-responsive gelation characteristics with the potential to control drug release according to specific therapeutic needs. This review discusses some of the most important plant-derived polymeric compounds that are used or investigated as excipients in drug delivery systems.

No description available.

No description available.

No description available.