Anionic conjugates of glycosylated bacterial metabolite

Abstract

The invention relates to anionic conjugates of glycosylated bacterial metabolites that may be used to mimic the structure and/or activity of the anionic bioactive molecules known as glycosaminoglycans (GAGs). The invention also relates to processes for the preparation of the conjugates. Such conjugates are useful in the prophylaxis and/or treatment of disease conditions and in particular chronic disease conditions such as inflammatory (including allergic) diseases, metastatic cancers and infection by pathogenic agents including bacteria, viruses or parasites.

1 . An anionic conjugate of 2 or more glycosylated bacterial metabolites, wherein prior to conjugation one or more of the metabolites is optionally modified. 
     
     
         2 . The conjugate according to  claim 1  wherein prior to conjugation one or more of the metabolites is optionally modified to facilitate conjugation. 
     
     
         3 . The conjugate according to  claim 1  wherein at least one of the glycosylated bacterial metabolites is a metabolite of an  actinobacter  or  bacillus  species. 
     
     
         4 . The conjugate according to  claim 1  wherein the glycosylated bacterial metabolites are selected from C 7 N cyclitol metabolites and aminoglycoside antibiotics 
     
     
         5 . The conjugate according to  claim 1  wherein at least one of the glycosylated bacterial metabolites is moenomycin. 
     
     
         6 . The conjugate according to  claim 1  wherein at least one of the glycosylated bacterial metabolites is polyhydroxylated. 
     
     
         7 . The conjugate according to  claim 6  wherein at least one of the hydroxyl groups is transformed into an anionic group. 
     
     
         8 . The conjugate according to  claim 7  wherein the anionic group is a sulfate or phosphate group. 
     
     
         9 . The conjugate according to  claim 1  wherein the glycosylated bacterial metabolites are conjugated by a linking group. 
     
     
         10 . The conjugate according to  claim 1  which is represented by formula I:
   M 1 L 1 M i L i  n−1 M n+1   (I)
 
 
       wherein: n is a positive integer;
 for a given n, there are n−1 successive values for i starting from 2 in the series 2, 3, . . . , n; 
 each M is independently a glycosylated bacterial metabolite or modified glycosylated bacterial metabolite; 
 the or each L is a linking group. 
 
     
     
         11 . A process for preparing an anionic conjugate of 2 or more glycosylated bacterial metabolites comprising the steps of:
 a) transforming at least one of the metabolites into an anionic derivative; and   b) conjugating the metabolites via a linking group;   
       wherein steps a) and b) may be performed in either order, and wherein one or more of the metabolites is optionally modified prior to step b). 
     
     
         12 . The process according to  claim 11  wherein step a) is performed prior to step b). 
     
     
         13 . The process according to  claim 11  wherein at least one of the glycosylated bacterial metabolites is a metabolite of an  actinobacter  or  bacillus  species. 
     
     
         14 . The process according to  claim 11  wherein the glycosylated bacterial metabolites are selected from C 7 N cyclitol metabolites and aminoglycoside antibiotics. 
     
     
         15 . The process according to  claim 11  wherein the glycosylated bacterial metabolites are moenomycin. 
     
     
         16 . The process according to  claim 11  wherein, when present, the step of modifying a metabolite prior to step b) comprises fragmentation of the metabolite. 
     
     
         17 . The process according to  claim 16  wherein the fragmentation of the metabolite comprises breaking at least one glycosidic linkage within the metabolite. 
     
     
         18 . The process according to  claim 11  wherein at least one of the metabolites is polyhydroxylated and step a) comprises transforming a hydroxyl group of the polyhydroxylated metabolite into a sulfate or phosphate group. 
     
     
         19 . A pharmaceutical composition comprising a therapeutically effective amount of the anionic conjugate according to  claim 1  and a pharmaceutically acceptable carrier and/or diluent. 
     
     
         20 . The use of the anionic conjugate according to  claim 1  in the manufacture of a medicament for the prophylaxis and/or treatment of inflammatory (including allergic) diseases, metastatic cancers or infection by pathogenic agents (including bacteria, viruses or parasites). 
     
     
         21 . A method of preventing and/or treating inflammatory (including allergic) diseases, metastatic cancers or infection by pathogenic agents (including bacteria, viruses or parasites) comprising administering an anionic conjugate according to any one of  claim 1  to a subject in need thereof.