Carbamate, thiocarbamate or carbamide comprising a biomolecular moiety

Abstract

Compounds are provided which comprise (a) at least two polymerisable moieties, (b) at least one amino acid residue of an amino acid comprising at least two amine groups of which at least two amine groups have formed a carbamate, a thiocarbamate or a carbamide group, and (c) a biomolecular moiety linked directly or via a spacer to the carboxylic acid moiety of the diamino acid residue or a carboxylic acid to which such moiety can be linked. A polymer obtained from such compounds is also disclosed.

1 . A formulation comprising:
 (a) a polymerizable compound comprising (a) at least two radically polymerizable moieties comprising an acrylate, an alkylacrylate, a methacrylate, an alkylmethacrylate, a vinylether, a fumarate, a vinylsulphone, or an itaconate, (b) at least one amino acid residue of an amino acid, the amino acid comprising at least two amine groups, and (c) a biomolecular moiety Z linked directly or via a spacer to the amino acid residue via a carboxylic acid moiety of the amino acid, wherein the polymerizable compound comprises at least two carbamate groups, at least two carbamide groups, or at least one carbamate group and at least one carbamide group, wherein the at least two carbamate groups, at least two carbamide groups, or at least one carbamate group and at least one carbamide group result from the reaction of an amine group of the amino acid with one or more other compounds; and   (b) a photo-initiator.   
     
     
         2 . The formulation according to  claim 1 , wherein the polymerizable compound further comprises a polyester, a polythioester, a polyorthoester, a polyamide, a polythioether, a polyanhydride, a polydioxanone, or a polycarbonate moiety. 
     
     
         3 . The formulation according to  claim 1 , further comprising (c) a further polymerizable compound comprising a polymerizable moiety comprising an acrylate, an alkylacrylate, a methacrylate, an alkylmethacrylate, a vinylether, a fumarate, a vinylsulphone, or an itaconate, wherein the further polymerizable compound is able to copolymerize with the polymerizable compound. 
     
     
         4 . The formulation according to  claim 2 , further comprising (c) a further polymerizable compound comprising a polymerizable moiety comprising an acrylate, an alkylacrylate, a methacrylate, an alkylmethacrylate, a vinylether, a fumarate, a vinylsulphone, or an itaconate, wherein the further polymerizable compound is able to copolymerize with the polymerizable compound. 
     
     
         5 . The formulation according to  claim 3 , wherein the polymerizable compound and the further polymerizable compound each comprise an acrylate or methacrylate group. 
     
     
         6 . The formulation according to  claim 1 , wherein the at least two radically polymerizable moieties are endgroups of the polymerizable compound. 
     
     
         7 . The formulation according to  claim 1 , wherein the amino acid residue is a residue of lysine, ornithine, hydroxylysine, N-alpha-methyl lysine, or diaminobutanoic acid. 
     
     
         8 . The formulation according to  claim 1 , wherein the amino acid residue is a residue of L-lysine, L-hydroxylysine, or N-alpha-methyl-lysine. 
     
     
         9 . The formulation according to  claim 1 , wherein the biomolecular moiety Z is a peptide residue. 
     
     
         10 . The formulation according to  claim 1 , wherein the biomolecular moiety Z comprises a peptide residue comprising the sequence RGD, GRGDS, RGDS, YIGSR, REDV, GTPGPQGIAGQRGW, PDGEA, KRSR, or NSPVNSKIPKACCVPTELSAI. 
     
     
         11 . The formulation according to  claim 1 , wherein the biomolecular moiety Z comprises heparin. 
     
     
         12 . The formulation according to  claim 1 , wherein the biomolecular moiety Z comprises a signaling moiety for a cell. 
     
     
         13 . The formulation according to  claim 2 , wherein the biomolecular moiety Z comprises a peptide residue comprising the sequence RGD, GRGDS, RGDS, YIGSR, REDV, GTPGPQGIAGQRGW, PDGEA, KRSR, or NSPVNSKIPKACCVPTELSAI. 
     
     
         14 . The formulation according to  claim 8 , wherein the biomolecular moiety Z YIGSR, REDV, GTPGPQGIAGQRGW, PDGEA, KRSR, or NSPVNSKIPKACCVPTELSAI, or the biomolecular moiety Z comprises heparin. 
     
     
         15 . A method of forming an article comprising the step of polymerizing the formulation according to  claim 3 . 
     
     
         16 . An article formed by polymerizing the formulation according to  claim 3 . 
     
     
         17 . An article formed by polymerizing the formulation according to  claim 8 . 
     
     
         18 . A formulation comprising:
 (a) A compound according to Formula I:   
       
         
           
           
               
               
           
         
       
       wherein
 G is a residue of a —OH, —NH 2 , or —RNH multifunctional polymer or oligomer comprising a polyester, a polythioester, a polyorthoester, a polyamide, a polythioether, a polyanhydride, a polydioxanone, or a polycarbonate, wherein R is as defined below, or G is an X as defined below; 
 each X independently represents an acrylate or a methacrylate; 
 each Y independently represents, O or NR; 
 each R independently represents hydrogen or a group selected from substituted and unsubstituted hydrocarbons which optionally contain one or more heteroatoms; 
 L represents a substituted or unsubstituted hydrocarbon that optionally contains one or more heteroatoms; 
 n is an integer having a value of 1 if G is an X, and n is at least 2 if G represents a residue of the multifunctional polymer or oligomer; and 
 Z is a biomolecular moiety linked directly or via a spacer to the remainder of the compound; and 
 (b) a photo-initiator. 
 
     
     
         19 . A compound according to  claim 18 , wherein the NR-L(C═O)—NR moiety of Formula I represents the residue of a lysine moiety, a hydroxylysine moiety, or an N-alpha-methylated lysine moiety. 
     
     
         20 . An article formed by polymerizing the formulation according to  claim 19 .