Epitopes formed by non-covalent association of conjugates

Abstract

A method for producing and using in treatment a composition for interacting with a ligand, which composition comprises a non-covalent association of a plurality of distinct conjugates, each conjugate comprising a head group and a tail group, wherein the tail groups of the conjugates form a hydrophobic aggregation and the conjugates are movable within the association so that, in the presence of a ligand, at least two of the head groups are appropriately positioned to form an epitope capable of interacting with the ligand more strongly than each of the head groups individually.

1 . A method for producing a composition for interacting with a ligand, which method comprises:
 (a) providing a plurality of distinct conjugates, each conjugate comprising a head group and a tail group;   and   (b) forming from the plurality of conjugates a non-covalent association thereof, in which the tail groups aggregate hydrophobically and in which the conjugates are movable so that, in the presence of a ligand, at least two of the head groups are appropriately positioned to form an epitope capable of interacting with the ligand more strongly than each of head groups individually.   
     
     
         2 . The method of  claim 1 , wherein the head group is selected from the group consisting of an amino acid, a peptide, a peptide analogue, a monosaccharide, a polysaccharide, a mononucleotide, a polynucleotide, a sterol, a water-soluble vitamin, a porphyrin nucleus, a haem nucleus, a metal ion chelate, a water-soluble drug, a hormone, and an enzyme substrate. 
     
     
         3 . The method of  claim 2 , wherein the head group comprises an amino acid. 
     
     
         4 . The method of  claim 3 , wherein the head group comprises a peptide. 
     
     
         5 . The method of  claim 3  or  claim 4 , wherein the amino acid comprises a terminal amino acid selected from the group consisting of hydrophilic amino acids, hydroxylic amino acids, acidic amino acids, amide amino acids, basic amino acids, and aromatic amino acids. 
     
     
         6 . The method of  claim 1 , wherein the tail group comprises a lipophilic group selected from the group consisting of a straight chain fatty acid, a branched-chain fatty acid, an alcohol having at least 8 carbon atoms, an aldehyde having at least 8 carbon atoms, a lipidic amino acid analogue, a prostaglandin, a leukotriene, a monoglyceride, a diglyceride, a sterol, a sphingosine derivative, a ceramide derivative, a silicon-substituted derivative thereof, and a halogen-substituted derivative thereof. 
     
     
         7 . The method of  claim 6 , wherein the lipophilic group comprises a C 10  to C 14  fatty acid. 
     
     
         8 . The method of  claim 1 , wherein the conjugate further comprises a spacer group linking the head group to the tail group. 
     
     
         9 . The method of  claim 8 , wherein the spacer group is hydrophilic. 
     
     
         10 . The method of  claim 9 , wherein the spacer group comprises an amino acid, a hydroxy acid, a sugar or a polyethylene glycol. 
     
     
         11 . The method of  claim 1 , wherein the non-covalent association comprises a lamellar structure, a micelle or a liposome. 
     
     
         12 . The method of  claim 1 , wherein the step of providing the plurality of conjugates comprises:
 (a) selecting a set of conjugates with an array of head groups;   (b) forming a non-covalent association therefrom, in which the tail groups aggregate hydrophobically and in which the conjugates are movable;   (c) assaying for sufficient interaction between the non-covalent association and the ligand;   (d) optionally repeating steps (a) to (c) using a set of conjugates with a modified array of head groups; and   (e) on finding sufficient interaction in step (c) selecting the set of conjugates as the plurality of conjugates in step (a).   
     
     
         13 . The method of  claim 12 , wherein the array of head groups comprises (a) at least one terminal amino acid from each of the following classes of amino acid:
 hydrophobic amino acids, hydroxylic amino acids, acidic amino acids and amide amino acids; and (b) at least two further terminal amino acids comprising at least one basic amino acid and at least one aromatic amino acid, or at least two basic amino acids or aromatic amino acids.   
     
     
         14 . The method of  claim 13 , wherein the modified array of head groups used in step (d) comprises the array of head groups used in steps (a) to (c) in which the at least two further terminal amino acids are different from those used in steps (a) to (c). 
     
     
         15 . The method of  claim 12 , wherein the array of head groups comprises at least one terminal amino acid from each of the following classes of amino acid: hydrophobic amino acids, hydroxylic amino acids, acidic amino acids, amide amino acids, basic amino acids and aromatic amino acids. 
     
     
         16 . The method of  claim 15 , wherein the modified array of head groups used in step (d) comprises the array of head groups used in steps (a) to (c) in which the at least one terminal amino acid from one of the classes of amino acid is either absent or replaced by a charged version thereof. 
     
     
         17 . A method for producing a molecule for interacting with a ligand, comprising:
 (a) producing a composition according to the method of  claim 1 ;   (b) identifying the at least two head group which form an epitope for the ligand in the composition; and   (c) producing a molecule incorporating the functional groups of the at least two head groups optionally spaced apart by one or more linker groups so that the molecule is capable of interacting with the ligand more strongly than each of the head groups individually.   
     
     
         18 . A method of treating a disease comprising administering to a patient isolated micelles which comprise a plurality of conjugate molecules non-covalently associating with one another to form the micelles, each conjugate molecule comprising (1) a head group molecule conjugated to a hydrophobic tail group molecule, optionally via a spacer molecule, (2) a surface formed by the head group molecules, which surface comprises a plurality of distinct non-covalent associations of the head group molecules, and (3) a hydrophobic core formed by the hydrophobic tail group molecules; wherein the head group molecules in the non-covalent associations change configuration through the movement of the head group molecules on or along the surface, and the movement of the head group molecules is facilitated by the movement of the conjugate molecules in the micelle, and wherein a distinct non-covalent association of the head group molecules forms an epitope which has higher affinity to a ligand than each of the head groups of the conjugates individually does. 
     
     
         19 . The method of  claim 18  wherein the head group of the micelles is selected from the group consisting of an amino acid, a peptide, a peptide analogue, a monosaccharide, a polysaccharide, a mononucleotide, a polynucleotide, a sterol, a water-soluble vitamin, a porphyrin nucleus, a haem nucleus, a metal ion chelate, a water-soluble drug, a hormone, and an enzyme substrate. 
     
     
         20 . The method of  claim 19  wherein the head group comprises an amino acid. 
     
     
         21 . The method of  claim 20 , wherein the head group comprises a peptide. 
     
     
         22 . The method of  claim 20  or of  claim 21 , wherein the amino acid comprises a terminal amino acid selected from the group consisting of hydrophilic amino acids, hydroxylic amino acids, acidic amino acids, amide amino acids, basic amino acids, and aromatic amino acids. 
     
     
         23 . The method of  claim 18 , wherein the tail group comprises a lipophilic group selected from the group consisting of a straight chain fatty acid, a branched-chain fatty acid, an alcohol having at least  8  carbon atoms, an aldehyde having at least  8  carbon atoms, a lipidic amino acid analogue, a prostaglandin, a leukotriene, a monoglyceride, a diglyceride, a sterol, a sphingosine derivative, a ceramide derivative, a silicon-substituted derivative thereof, and a halogen-substituted derivative thereof. 
     
     
         24 . The method of  claim 23 , wherein the lipophilic group comprises a C 10  to C 14  fatty acid. 
     
     
         25 . The method according to  claim 18 , wherein the conjugate further comprises a spacer group linking the head group to the tail group. 
     
     
         26 . The method according to  claim 25 , wherein the spacer group is hydrophilic. 
     
     
         27 . The method according to  claim 26 , wherein the spacer group comprises an amino acid, a hydroxy acid, a sugar or a polyethylene glycol.