COMPOSITIONS CONTAINING AN ALPHA 1,2-FUCOSE LINKAGE AND USES THEREOF

• US 20020019991A1
• Filed: 04/30/1998
• Published: 02/14/2002
• Est. Priority Date: 04/30/1998
• Status: Abandoned Application

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: RUIZ-PALACIOS, GUILLERMO M., PRIETO, PEDRO A.
• Application Number:
  US09/070,177
• Publication Number:
  US 20020019991A1
• Time in Patent Office: Days
• US Class Current: 800/3
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 31/702 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
• CPC Class Codes: A61K 31/7024 Esters of saccharides
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The subject intention relates to compositions containing at least one fucose residue in an α1-2 linkage and uses thereof. In particular, such compositions can be used in the treatment and prevention of gastrointestinal infections caused by, for example, Escherichia coil and Vibrio cholerae. The subject invention also encompasses methods of screening for the above compositions. Additionally, the subject invention includes vaccines.

Claims

1. A pharmaceutical composition comprising at least one fucose residue in an α

1-2 linkage and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 wherein said at least ore fucose residue in an α

1-2 linkage is present in a compound selected from the group consisting of 2′

-fucosyllactose, difucosyllactose, Fucα

1-2Galβ

1-4[Fucα

1-3]Glc, glycoproteins or glycodeptides containing the structure Fucα

1-2Galβ

1-4Glc Nac 31-3 GM-Fuc (Fucα

1-2Galβ

1-3GalNac), glycolipids and fucosylated derivatives of neutral glycolipids.

6. A rehydration solution comprising said composition of claim 1 or claim 3.

12. The method of claim 1 wherein said host cell receptor comprises a fucosylated blood group antigen.

3. A nutritional composition comprising at least one fucose residue In an α

1-2 linkage, at least one protein not found in human breast milk, and at least one member selected from the group consisting of an edible fat, a carbohydrate, a protein, a vitamin and a mineral.

4. The nutritional composition of claim 3 wherein said at least one fucose residue in an α

1-2 linkage is present in a compound selected from the group consisting of 2′

-fucosyllactose, difucosyllactose, Fucα

1-2Galβ

1-4[Fucα

1-3]Glc, glycoproteins or glycopeptides containing the structure Fucα

1-2Galβ

1-4Glc Nac β

1-3 GMj-Fuc (Fucα

1-2Galβ

1-3GalNac), glycolipids and fucosylated derivatives of neutral glycolipids.

5. The nutritional composition of claim 4 wherein said composition is an infant formula.

7. A method of preventing or treating diarrhea or enterocolitis in a patient comprising administering a composition comprising at least one fucose residue in an α

1-2 linkage to a patient in need of said prevention or treatment, said composition being administered in an amount sufficient to effect said treatment of prevention.

8. The method of claim 7 wherein said composition is administered to a human or to an animal.

9. The method of claim w Wherein said diarrhea or enterocolitis is caused by a microorganism selected from the group consisting of Escherichia coli and Vibrio cholerae.

10. The method of claim 9 wherein said enterocolitis is necrotic enterocolitis.

11. A method of screening for a composition which prevents the attachment of E. coli or V. cholerae to a host cell receptor comprising the steps of:

a) exposing said composition in question to said host cell receptor;

b) adding Escherichia coli or Vibrio cholerae to said composition of step (a) and said host cell receptor; and

c) determining whether Inhibition of binding of said cells to said host cell receptor occurs, said inhibition indicating the presence of a composition which binds to said host cell receptor and prevents attachment of said E. coli or V. cholerae to said host cell receptor.

13. The method of claim 12 wherein said fucosylated blood group antigen is H-2.

15. The vaccine of claim 14 wherein said vaccine is administered subcutaneously or Intramuscularly.

14. A vaccine comprising at least one protein which binds to at least one fucose residue in an α

1-2 linkage and a physiologically acceptable adjuvant.

16. A method of screening for a composition which prevents the attachment of E. coli or V. cholerae to a mammalian cell receptor comprising the steps of:

a) constructing a transgenic mammalian embryo which, upon birth, produces a composition comprising at least one fucose residue in an α

1-2 linkage;

b) implanting said trangenic mammalian embryo into a recipient adult female;

c) allowing gestation and birth to occur;

d) challenging said resulting mammal with E. coli or V. cholerae;

and

e) determining whether infection develops in said resulting mammal, lack of infection indicating that said composition expressed by said resulting mammal prevents attachment of E. coli or V. cholerae to said receptor of said resulting mammal.

17. A method of screening for a composition which prevents the attachment of E. coli or V. cholerae to a host cell receptor comprising the steps of:

a) exposing transfected, mammalian cells expressing a neoglyconjugate to E. coli or V. cholerae;

b) determining whether binding has occurred between said mammalian cells and said E. coli or V. cholerae, a high degree of binding inhibition relative to a control indicating that said neoglyconjugate presents attachment of said E. coli or V. cholerae to said receptor of said mammalian cells.

18. A method of screening for a composition which prevents the attachment of E. coli or V. cholerae to a host cell receptor comprising she seeps of:

a) purifying a glycoconjugate comprising at least one fucose residue in an α

1-2 linkage from a mammalian cell;

b) immobilizing said glycoconjugate on a solid support;

c) exposing said immobilized glycoconjugate to E. coli cells or V. cholerae cells;

d) adding a composition of interest to said immobilized glycoconjugate and E. coli cells or V. cholerae cells;

d) determining whether binding occurs between said immobilized glycoconjugate and said E. coli cells or V. cholerae cells, lack of binding indicating a composition which prevents the attachment of E. coli cells or V. cholerae cells to a host cell receptor.

19. A method c screening for a composition which prevents the attachment of E. coli or V. cholerae to a receptor of mammalian cells comprising the steps of:

a) constructing a transgenic, mammalian embryo which, after birth, produces a composition comprising at least one fucose residue in an α

1-2 linkage;

b) implanting said transgenic, mammalian embryo into a recipient female;

c) allowing gestation and birth to occur;

d) allowing said resulting transgenic mammal to mate and produce offspring;

e) allowing said offspring to suckle on milk produced by said transgenic mammals;

f) challenging said offspring with E. coli cells or V. cholerae cells;

g) determining whether infection occurs, lack of infection indicating a composition present in said milk of said transgenic mammal which prevents the attachment of E. coli or V. cholerae to a receptor of cells of said offspring.

20. A method of screening pathogenic microorganisms from non-pathogenic microorganisms comprising the steps of:

a) isolating a microorganism of interest;

b) exposing said microorganism to a glyconjugate receptor comprising at least one fucose residue in an α

1-2 linkage, wherein said receptor binds only to pathogenic microorganisms; and

c) determining whether binding occurs between said glycoconjugate receptor and said microorganism of interest, binding indicating that said microrganism is pathogenic and non-binding indicating that said microorganism is non-pathogenic.