Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1998-08-07
1999-10-05
Lee, Howard C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
424DIG16, 514 53, 514 61, A61K 3170, A61K 3174, A61K 31745, A61K 31785
Patent
active
059624230
ABSTRACT:
Compounds which bind to shiga-like toxins (SLT) associated with enteric E. coli infection, compositions including the compounds, methods for the neutralization of (SLT) in a patient, and methods for the diagnosis of enteric E. coli infection are disclosed. The compounds include a core molecule bound to a plurality of linker arms, which in turn are bound to a plurality of bridging moieties, which in turn are bound to two or three di- or tri-saccharide moieties. The di- or tri-saccharide moieties themselves are active in binding to the SLTs. The presence of a plurality of bridged dimers of the di- and tri-saccharides is responsible for the increased binding affinity of the compounds relative to the di- and tri-saccharides themselves. The compounds, when administered in a timely fashion to a patient suffering from enteric E. coli infection, inhibit progression of this infection into hemolytic uremic syndrome (HUS).
REFERENCES:
patent: 4137401 (1979-01-01), Lemieux et al.
patent: 4238473 (1980-12-01), Lemieux et al.
patent: 4362720 (1982-12-01), Lemieux et al.
patent: 5041516 (1991-08-01), Frechet et al.
patent: 5079353 (1992-01-01), Ratcliffe et al.
patent: 5527524 (1996-06-01), Tomalia et al.
patent: 5620858 (1997-04-01), Armstrong et al.
patent: 5679653 (1997-10-01), Armstrong et al.
patent: 5714166 (1998-02-01), Tomalia et al.
patent: 5807971 (1998-09-01), Gozzini et al.
patent: 5834020 (1998-11-01), Margerum et al.
Abbas, S.A., et al., "Tumor-Associated Oligosaccharides I: Synthesis of Sialyl-Lewis.sup.a Antigenic Determinant," Sialic Acids Proc. Japan-German Symp. Berlin, pp. 22-23 (1988).
Altman, D.G., "Comparing groups-continuous data," Practical Statistics for Medical Research, 1st ed., New York, Chapman and Hall: pp. 179-228 (1991).
Amvam-Zollo, et al., "Streptococcus pneumoniae Type XIV Polysaccharide: Synthesis of a Repeating Branched Tetrasaccharide with Dioxa-Type Spacer Arms," Carbohy. Res., vol. 150 pp. 199-212 (1986).
Armstrong, et al., "Maintenance of Biological Activity of Pertussis Toxin Radioiodinated While Bound to Fetuin-Agarose," Infect. Immun., vol. 55, pp. 1294-1299 (1987).
Armstrong, et al., "Investigation of Shiga-like Toxin Binding to Chemically Synthesized Oligosaccharide Sequences," J. Infect Dis., vol. 164, pp. 1160-1167 (1991).
Boyd, et al., "Vertoxdin Receptor Glycolipid in Human Renal Tissue," Nephron, vol. 51, pp. 207-210 (1989).
Calderwood, et al., Nucleotide sequence of the Shiga-like toxin genes of Escherichia coli, Proc. Natl. Acad. Sci. (USA), vol. 84, pp. 4364-4368 (1987).
Chernyak, Y.A., et a., "A New Type of Carbohydrate-Containing Synthetic Antigen: Synthesis of Carbohydrate-Containing Polyacrylamide Copolymers having the Specificity of 0:3 and 0:4 Factors of Salmonella," Carbo. Res., vol. 128, pp. 269-282 (1984).
Cimolai, et al., The Journal of Pediatrics, vol. 117 pp. 676 (1990).
Cohen, et al., "Roles of Globotriosyl- and Galabiosylceramide in Verotoxin Binding and High Affinity Interferon Receptor," J. Biol. Chem., vol. 262, pp. 17088-17091 (1987).
Cox, et al., "A New Synthesis of 4-0-.alpha.-D-Galactopyranosyl-D-Galacto-Pyranose," Carbohy. Res., vol. 62, pp. 245-252 (1978).
Dahmen, J., et al., "Synthesis of Spacer-Arm, Lipid, and Ethyl Glycosides of the Trisacchride Portion Blood-Group P.sup.k Antigen: Preparation of Neoglycoproteins," Carboh. Res., vol. 127, pp. 15-25 (1984).
Dahmen, J., et al., "2-Bromoethyl glycosides: applications in the synthesis of spacer-arm glycosides," Carboh. Res., vol. 118, pp. 292-301 (1983).
DeGrandis, et al., "Globotetraosylceramide is Recognized by the Pig Edema Disease Toxin," J. Biol. Chem., vol. 264, pp. 12520-12525 (1989).
Ekborg, G., et al., "Synthesis of Three Disacharides for the Preparation of Immunogens bearing Immunodeterminants Known to Occur on Glycoproteins," Carboh. Res., vol. 110, pp. 55-67 (1982).
Fernandez-Santana, V., et al., "Glycosides of Monoallyl Diethylene Glycol. A New Type of Spacer Group for Synthetic Oligosaccharides," J. Carboh. Chem., vol. 8, No. 3, pp. 531-537 (1989).
Fugedi, P., et al., "Thioglycosides as Glycosylating Agents in Oligosaccharide Synthesis," Glycoconjugate J., vol. 4, pp. 97-108 (1987).
Gannon, et al., "Molecular cloning and nucleotide sequence of another variant of the Escherichia coli Shiga-like toxin II family," J. Gen. Microbiol., vol. 136, pp. 1125-1135 (1990).
Garegg, P.J., et al., "A Synthesis of 8-Methoxycarbonyloct-1-yl O-.alpha.-D-Galactopyranosyl-(1.fwdarw.3)-O-.beta.-D-Galactopyranosyl-(1.f wdarw.4)-2-Acetamido-2-Deoxy-.beta.-D-Glucopyranoside," Carboh. Res., vol. 136, pp. 207-213 (1985).
Garegg, P.J., et al., "Synthesis of 6- and 6'-deoxy derivatives of methyl 4-O-.alpha.-D-galactopyranosyl-.beta.-D-Galactopyranoside for studies of inhibition of pyelonephritogenic fimbriated E. coli adhesion to urinary epithelium-cell surfaces," Carboh. Res., vol. 137, pp. 270-275 (1985).
Hansen, et al., "Di-, Tri-, and Tetravalent Dendritic Galabiosides That Inhibit Hemagglutination by Streptococcus suis at Nanomolar Concentration," J. Am. Chem. Soc., vol. 119, pp. 6974-6979 (1997).
Head, S., et al., "Modification of the Glycolipid-Binding Specificity of Vero Cytotoxin by Polymyxin B and Other Cyclic Amphipathic Peptides," Infect. Immunol., vol. 58, pp. 1532-1537 (1990).
Head, S., et al., "Purification and characterization of verocytotoxin 2," FEMS Microbiol. Lett., vol. 51, pp. 211-216 (1988).
Ito, et al., "Cloning and nucleotide sequencing of Vero toxin 2 variant genes from Escherichia coli O91:H21 isolated from patient . . ." Microb. Pathog., vol. 8 pp. 47-60 (1990).
Jacewicz, et al., "Pathogenesis of Shigella Diarrhea," J. Exp. Med., vol. 163, pp. 1391-1404 (1986).
Jackson, et al., "Nucleotide sequence analysis of the structural genes for Shiga-like toxin I encoded by bacteriophage 933J . . . ," Microb. Pathog., vol. 2 pp. 147-153 (1987).
Jacquinet, et al., "Synthesis of Blood-group Substances, Part 11. Synthesis of the Trisaccharide O-.alpha.-D-Galactopyranosyl-(1.fwdarw.3)-O-.beta.-D-Galactopyranosyl-(1.f wdarw.4)-2-. . . ," J.C.S. Perkin, vol. I, pp. 326-330 (1981).
Kameyama, et al., "Total synthesis of sialyl Lewis X," Carboh. Res., vol. 209 pp. c1-c4 (1991).
Karmali, et al., "Sensitive Method for Detecting Low Numbers of Verotoxin-Producing Escherichia coli in Mixed Cultures . . . ," J. Clin. Microbiol., vol. 22, pp. 614-619 (1985).
Koike, et al., "Total Synthesis of Globotriaosyl-E and Z-Ceramides and Isoglobotriaosyl-E-Ceramide," Carbohydr. Res., vol. 163, pp. 189-208 (1987).
Lee, et al., "Synthesis of 3-(2-Aminoethylthio)Propyl Glycosides," Carboh. Res., vol. 37, pp. 193-201 (1974).
Lemieux, et al., "The properties of a Synthetic Antigen Related to the Human Blood-Group Lewis A," J. Am. Chem. Soc., vol. 97, pp. 4076-4083 (1975).
Ling, et al., "Structure of the Shiga-like Toxin I B-Pentamer Complexed with an Analogue of Its Receptor Gb.sub.3," vol. 37, pp. 1777-1788 (1998).
Lindberg, et al., "Identification of the Carbohydrate Receptor for Shiga Toxin Produced by Shigella dysenteriae Type 1," J. Biol. Chem., vol. 262, pp. 1779-1785 (1987).
Lingwood, et al., "Glycolipid Binding of Purified and Recombinant Escherichia coli Produced Verotoxin in Vitro," J. Biol. Chem., vol. 262, pp. 8834-8839 (1987).
Nilsson, et al., "Immobilization of Reducing Sugars as Toxin Binding Agents," Bioconj. Chem., vol. 8, No. 4, pp. 466-471 (1997).
Nyholm, et al., "Two distinct binding sites for globotriaosyl ceramide on verotoxins: identification by molecular modelling . . . ," Chem. and Biol., vol. 3, pp. 263-275 (1996).
Okamoto, et al., "Glycosidation of Sialic Acid," Tetrahedron, vol. 47 pp. 5835-5857 (1990).
Oku, et al., "Purification and some properties of a Vero toxin from a human strain of Escherichia coli that is immunologically . . . ," Microb. Pathog., vol. 6, pp. 113-122 (1989).
Paulsen, H., "Advances in Selective Chemical Syntheses of Complex Oligosaccharides," Angew. Chem. Int. Ed. Eng., vol. 21, pp. 155-173 (1982).
Paulsen, H., et al., "Synthese Von Oligosaccharid-Determinanten Mit Amid-spacer Vom Typ Des T-Antigens," Carbohydr. Res., vol. 104, pp. 195-219
Armstrong Glen
Bundle David R.
Kitov Pavel
Ling Hong
Read Randy J.
Lee Howard C.
The Governors of the University of Alberta
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