Multimodal adsorption medium with multimodal ligands, method for the preparation and use thereof

Abstract

The present invention relates to a multimodal adsorption medium, in particular a multimodal chromatography medium, a method for its production, as well as use of the adsorption medium according to the invention or an adsorption medium produced according to the invention for the purification of biomolecules.

1 . A multimodal adsorption medium, comprising a polymeric carrier material C to which multimodal ligands of the following structure -G-(CO 2 H)n are covalently bonded via an —X—(C═O) group, 
       
         
           
           
               
               
           
         
       
       where X denotes —NR—, —O— or —S— and R denotes alkyl, alkenyl, aryl, heteroaryl or hydrogen, G denotes a group selected from the group composed of a branched or unbranched C 2-20  alkyl group, a substituted or unsubstituted C 3-10  cycloalkyl group, a branched or unbranched C 2-20  alkenyl group, a substituted or unsubstituted C 6-20  aryl group, and a substituted or unsubstituted C 4-20  heteroaryl group, wherein n is a whole number that is 1 or higher. 
     
     
         2 . The multimodal adsorption medium as claimed in  claim 1 , wherein the —X—(C═O) group is —NH—(C═O), 
     
     
         3 . The multimodal adsorption medium as claimed in  claim 1 , wherein the polymeric carrier material C comprises at least one material selected from the group composed of natural or synthetic fibers, (polymer) membranes, porous, polymeric monolithic molded bodies, polymer gels, films, nonwovens and wovens. 
     
     
         4 . The multimodal adsorption medium as claimed in  claim 1 , wherein the multimodal ligands are bound to the surface of the carrier material C via polymeric spacer elements. 
     
     
         5 . The multimodal adsorption medium as claimed in  claim 4 , wherein the polymeric spacer elements are polyamines with at least one primary amino group, which as an X—(C═O) bond forms an amide bond with the multimodal ligands, 
     
     
         6 . The multimodal adsorption medium of  claim 1 , wherein the G group is a branched or unbranched C 4-20  alkyl group or a branched or unbranched C 3-20  alkenyl group. 
     
     
         7 . The multimodal adsorption medium of  claim 1 , wherein the multimodal ligands have the following structure: 
       
         
           
           
               
               
           
         
       
       wherein G is a substituted or unsubstituted C 2-3  alkyl group, a substituted or unsubstituted C 3-10  cycloalkyl group, a substituted or unsubstituted C 2-3  alkenyl group, a substituted or unsubstituted C 6  aryl group or a substituted or unsubstituted five-membered or six-membered heteroaromatic group, wherein the substituents are selected from the group composed of a branched or unbranched C 1-10  alkyl group, a branched or unbranched C 2-10  alkenyl group, a C 6-20  aryl group, and a C 4-20  heteroaryl group. 
     
     
         8 . The multimodal adsorption medium as claimed in  claim 7 , wherein G denotes a branched or unbranched C 3-10  alkenyl group. 
     
     
         9 . The multimodal adsorption medium of  claim 1 , wherein the multimodal ligands have one of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein R′ is selected respectively from the group composed of hydrogen, F, Cl, Br, I, —OH, —NH 2 , SH, CO 2 H, a branched or unbranched C 1-10  alkyl group, a branched or unbranched C 2-10  alkenyl group, a C 6-20  aryl group, and a C 4-20  heteroaryl group, wherein A is a C 6  aryl group or a five-membered or six-membered heteroaromatic group, and wherein m is a whole number from 1 to 3. 
     
     
         10 . A method for producing an adsorption medium as claimed in  claim 1 , comprising the following steps:
 (a) providing a polymeric carrier material C, wherein the carrier material C has at least one —XH group that is reactive with carboxylic acid derivatives while forming a covalent bond —X—(C═O), where X denotes —NR—, —O— or —S— and R denotes alkyl, alkenyl, aryl, heteroaryl or hydrogen; and   (b) reacting the at least one —XH group of the polymeric carrier material C with a carboxylic acid derivative as a precursor of a multimodal ligand such that the covalent bond —X—(C═O) is formed via which the multimodal ligand is bonded to the carrier material C.   
     
     
         11 . The method as claimed in  claim 10 , wherein the covalent bond —X—(C═O) is a secondary amide bond that is formed by reacting a carboxylic anhydride as a precursor of the ligand and amine groups of the carrier material C, and wherein the multimodal ligand has at least one free carboxylic acid group. 
     
     
         12 . Use of the multimodal adsorption medium of  claim 1  or an adsorption medium produced by the method as claimed in  claim 10  for the purification of biomolecules. 
     
     
         13 . Use as claimed in  claim 12 , wherein the biomolecules are proteins, peptides, amino acids, nucleic acids, viruses, virus-like particles and/or endotoxins, 
     
     
         14 . Use as claimed in  claim 13 , wherein the proteins are antibodies. 
     
     
         15 . The multimodal adsorption medium of  claim 1 , wherein the G group denotes a group selected from the group composed of a branched or unbranched C 2-20  alkyl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one aromatic substituent, a substituted or unsubstituted C 3-10  cycloalkyl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one aromatic substituent, a branched or unbranched C 2-20  alkenyl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one aromatic substituent, a substituted or unsubstituted C 6-20  aryl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, and a substituted or unsubstituted C 4-20  oheteroaryl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, 
     
     
         16 . The multimodal adsorption medium of  claim 6 , wherein the G group denotes a group selected from the group composed of a branched or unbranched C 4-20  alkyl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one aromatic substituent, and a branched or unbranched C 3-20  alkenyl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one aromatic substituent. 
     
     
         17 . The multimodal adsorption medium of  claim 7 , wherein G is a substituted or unsubstituted C 2-3  alkyl group, a substituted or unsubstituted C 3-10  cycloalkyl group, a substituted or unsubstituted C 2-3  alkenyl group, a substituted or unsubstituted C 6  aryl group or a substituted or unsubstituted five-membered or six-membered heteroaromatic group, wherein the substituents are selected from the group composed of a branched or unbranched C 1-10  alkyl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one hydroxyl, carbonyl, carboxyl, carboxylic anhydride or aromatic substituent, a branched or unbranched C 2-10  alkenyl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one hydroxyl, carbonyl, carboxyl, carboxylic anhydride or aromatic substituent, a C 6-20  aryl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and at least one hydroxyl, carbonyl, carboxyl, or carboxylic anhydride substituent, and a C 4-20  heteroaryl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and at least one hydroxyl, carbonyl, carboxyl, or carboxylic anhydride substituent, and a hydroxy, thiol or amino group. 
     
     
         18 . The multimodal adsorption medium as claimed in  claim 17 , wherein G denotes a branched or unbranched C 3-10  alkenyl group that contains one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one hydroxyl, carbonyl, carboxyl, carboxylic anhydride or aromatic substituent. 
     
     
         19 . The multimodal adsorption medium of  claim 9 , wherein R′ is selected respectively from the group composed of hydrogen, F, Cl, Br, I, —OH, —NH 2 , SH, CO2H, a branched or unbranched C 1-10  alkyl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and/or optionally at least one hydroxyl, carbonyl, carboxyl, carboxylic anhydride or aromatic substituent, a branched or unbranched C 2-10  alkenyl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one hydroxyl, carbonyl, carboxyl, carboxylic anhydride or aromatic substituent, a C 6-20  aryl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and/or at least one hydroxyl, carbonyl, carboxyl, or carboxylic anhydride substituent, and a C 4-20  heteroaryl group containing one or a plurality of heteroatoms selected from O, S, N and halogens, and at least one hydroxyl, carbonyl, carboxyl, or carboxylic anhydride substituent, wherein A is a C6 aryl group or a five-membered or six-membered heteroaromatic group, and wherein m is a whole number from 1 to 3.