Labeling reactant

Abstract

This invention concerns novel labeling reactants suitable for labeling of a biospecific binding reactant using solid-phase synthesis. The novel reactants are derivatives of diethylenetriaminepentaacetic acid (DTPA), wherein a suitable group is linked to the DTPA molecule, thus allowing site specific introduction of the ligand of said derivatives to bioactive molecules on solid phase in an oligopeptide synthesizer.

1 . A labeling reactant of formula (I) 
       
         
           
           
               
               
           
         
         wherein: 
         -A- is a linker formed from one to ten moieties, each moiety being selected from the group consisting of phenylene, alkyl containing 1-12 carbon atoms, ethynediyl (—C≡C—), ethylenediyl (—C═C—), ether (—O—), thioether (—S—), amide (—CO—NH— and —NH—CO— and —CO—NR″ and —NR″-CO—), carbonyl (—CO—), ester (—COO— and —OOC—), disulfide (—SS—), diaza (—N═N—) and tertiary amine (—NR″—), wherein R″ represents an alkyl containing less than 5 carbon atoms; 
         R is independently —COOR′ or —CONHR′, wherein R′ is an alkyl of 1 to 4 carbon atoms, phenyl or benzyl, and wherein said phenyl or benzyl is substituted or unsubstituted; 
         Z is a transient protecting group; and 
         X is a carboxylic acid, or an organic or inorganic salt, active ester or acid halide thereof. 
       
     
     
         2 . The labeling reactant according to  claim 1 , wherein X is an active ester of carboxylic acid and said active ester of carboxylic acid is selected from the group consisting of an N-hydroxysuccinimido, p-nitrophenol and pentafluorophenol ester. 
     
     
         3 . The labeling reactant according to  claim 1 , wherein X is an acid halide and said acid halide is selected from the group consisting of chloride and fluoride. 
     
     
         4 . The labeling reactant according  claim 1 , wherein Z is selected from the group consisting of fluorenylmethoxycarbonyl (Fmoc), nitrobenzenesulfonyl (Ns), tert-butoxycarbonyl (Boc) and 1,1-dioxobenzo[b]thiophen-2-ylmethyloxycarbonyl (Bsmoc). 
     
     
         5 . The labeling reactant according to  claim 1 , wherein the labeling reactant is penta-tert-butyl 2-{4′-{2-[4-carboxy-4-fluorenyl methyloxycarbonylamino)]butyrylamido}benzyl}diethylenetriamine-pentakis(acetate). 
     
     
         6 . A biospecific binding reactant labeled with the labeling reactant according to  claim 1 , wherein the biospecific labelling reactant is selected from the group consisting of an oligopeptide, protein, oligosaccaride, polysaccaride, phospholipid, PNA, LNA, antibody, hapten, drug, receptor binding ligand and lectine.