Syntheses of Model Compounds Related to an Antigenic Epitope in Pectic Polysaccharides from Bupleurum falcatum L. (II)

Abstract

The roots of Bupleurum falcatum L. (Japanese name Saiko) have been used in Chinese and Japanese herbal medicines for the treatment of chronic hepatitis, nephrosis syndrome, and autoimmune diseases. Yamada et al. 1) and Sun et al.2) reported that a potent antiulcer pectic polysaccharide (Bupleuran 2IIc) was isolated from the hot-water extract of the roots. Bupleuran 2IIc consists of a galacturonan region, a "ramified" region (PG-1) composed of a rhamnogalacturonan core with neutral sugar side chains, and a rhamnogalacturonan II-like region 3) ; the ramified region has been considered important for the expression of immunopharmacologic activity (Fig. 1). We reported in our previous paper 4) that the synthetic model compound shows specific activity. On the other hand, a polyclonal antibody (antibupleuran 2IIc/PG-1-IgG) against the ramified region of bupleuran 2IIc (antibupleuran 2IIc/PG-1-IgG) was prepared, and the antigenic epitopes were characterized to be 6-linked galactosyl chains with either GlcA or 4-O-Me-GlcA as a nonreducing terminal.5) Bupleuran 2IIc has mitogenic activity in the murine spleen and Peyer's patch cells, and the mitogenic activity was reduced in the presence of the antipolysaccharide antibody (antibupleuran 2IIc/PG-1-IgG). The mitogenic activity of bupleuran 2IIc was reduced with the addition ofwhich are a part of the epitopes of antibupleuran 2IIc/PG-1-IgG.6) The proposed structure of the antigenic epitopes in PG-1 has been a target for the synthetic studies in our laboratory. Despite the specificity of the binding, it is known that polysaccharide chains generally interact with their protein receptors as a natural cluster. This explains why the binding affinity of a synthetic model compound to the active site is low in various cases.7) Construction of a glycocluster aimed at their bioactive augmentation is an important problem in glycoscience. 9) However, it did not led to a marked augmentation (data not shown). Meanwhile, we developed new peptidic glycoclusters and a glycodendron, which consist of a b-alanine derivative and Minamiooya, Machida, Tokyo 194-8511, Japan: and c Oriental Medicine Research Center, Kitasato Institute; 5-9-1 Shiroganedai, Minato-ku, Tokyo 108-8642, Japan. Received October 12, 2005; accepted December 28, 2005 Stereocontrolled syntheses of model compounds related to a major antigenic epitope against antibupleurum 2IIc/PG-1-IgG from antiulcer pectic polysaccharide are described. A trisaccharide derivative (13) was prepared as a precursor and a novel and simple approach for the rational design of a glycocluster and glycodendrimer was developed, through the syntheses of the fluorescence-labeled glycocluster (2) and glycodendrimer (3).

From Glycopeptides to Glycopeptoids

“…The preparation of β‐peptoid‐based glycoclusters and glycodendrons has been thoroughly investigated by Takeda and co‐workers (although the terms “glycopeptoid” or even “peptoid” were not employed in their publications) 51–55. The glycocluster 70 is a representative example of non‐symmetrical structures that were synthesised (Figure 10).…”

“…For this purpose, various protected monomers ( 68 and 69 ) with spacers based on glycine, β‐alanine or GABA were formed, prior to their oligomerisation under coupling conditions mediated by diethyl cyanophosphonate. This approach to modular glycoclusters was employed, for example, for synthesising model compounds related to a major antigenic epitope against anti‐bupleurum 2IIc/PG‐1‐IgG from an anti‐ulcer pectic polysaccharide 55…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for the period 2005–2006

“…These include monosaccharides (Gao et al, 2005b;Lu, Fraser-Reid, & Gowda, 2005;Dubber et al, 2006a;Dubber, Sperling, & Lindhorst, 2006), cyclodextrins (Carpenter & Nepogodiev, 2005;Furuike et al, 2005;Gómez-García et al, 2005;Hattori et al, 2006;Yamanoi et al, 2005), calix [4]arenes (48) (ten Cate et al, 2005;Hocquelet et al, 2006), carbosilanes , phthalocyanines (49) (Alvarez-Mico et al, 2006), poly(amidoamine) (PAMAM) (Ibey et al, 2005;Kubler-Kielb & Pozsgay, 2005;Mangold et al, 2005;Wolfenden & Cloninger, 2005;Wolfenden & Cloninger, 2006;Zhu & Marchant, 2006), peptides (Hada et al, 2005;Jin et al, 2006;Kantchev, Chang, & Chang, 2006;Sato, Hada, & Takeda, 2006), pentaerythritol (2/33) (Xue et al, 2005;Al-Mughaid & Grindley, 2006), porphyrins (50) (Laville et al, 2006;Sol et al, 2006), trihydroxybenzoic acid (51) (Fernandez-Megia et al, 2006;Joosten et al, 2006), and trimesic acid (4/61) .…”

Design, Synthesis and Potent Pharmaceutical Applications of Glycodendrimers:A Mini Review

“…Takeda and coworkers designed an efficient synthetic strategy in glycoconjugate chemistry [55]. The trisaccharide derivative used as a precursor in this study was attached to a bifunctional linker to prepare the glycocluster by a convergent approach (Fig.…”