Oligomers and oligomeric segments of alpha-hydroxy carboxylic acids and alpha-amino acids

Abstract

An enzymatic synthesis and composition of α-hydroxy carboxylic acid and α-amino acid or peptide co-oligomers is disclosed wherein a residue of the α-hydroxy carboxylic acid is linked to a residue of the α-amino acid or peptide by an amide linkage. Proteolytic enzyme papain catalyzes co-oligomerization of the α-hydroxy carboxylic acid and α-amino acid. The degree and distribution of oligomerization varies upon the type and concentrations of different reaction mixtures utilized and upon the length of allowed reaction time. The resultant oligomers may be provided to ruminants as bioavailable amino acid supplements that are resistant to degradation in the rumen.

What is claimed is:  
     
         1 . A process for the preparation of an oligomer, the process comprising 
 preparing a mixture containing (i) an enzyme, (ii) an α-hydroxy carboxylic acid and (iii) an α-amino acid, the α-hydroxy carboxylic acid and the α-amino acid each being present in the mixture as a free acid, acid halide, amide, ester or anhydride independently of the other, and    forming an oligomer in the mixture, the oligomer containing a residue of the α-hydroxy carboxylic acid linked to a residue of the α-amino acid by an amide linkage.    
     
     
         2 . The process of  claim 1  wherein the α-hydroxy carboxylic acid is 2-hydroxy-4-(methylthio)butyric acid.  
     
     
         3 . The process of  claim 1  wherein the α-hydroxy carboxylic acid is 2-hydroxy-4-(methylthio)butyric acid and the α-amino acid is methionine.  
     
     
         4 . The process of  claim 1  wherein the α-hydroxy carboxylic acid is 2-hydroxy-4-(methylthio)butyric acid and the mixture comprises at least two α-amino acids.  
     
     
         5 . The process of  claim 4  wherein the mixture comprises methionine and lysine.  
     
     
         6 . The process of  claim 1  wherein the α-amino acids are selected from one or more essential α-amino acids.  
     
     
         7 . The process of  claim 6  wherein the α-amino acids are selected from the group consisting of isoleucine, phenylalanine, leucine, lysine, methionine, threonine, tryptophan, histidine, and valine.  
     
     
         8 . The process of  claim 1  wherein the enzyme is a protease.  
     
     
         9 . The process of  claim 1  wherein the enzyme is a protease selected from the group consisting of papain, subtilisin, thermolysin, α-chymotrypsin, and alkaline protease.  
     
     
         10 . The process of  claim 1  wherein the mixture is an aqueous solution.  
     
     
         11 . The process of  claim 1  wherein the mixture comprises an aqueous phase and an organic solvent phase.  
     
     
         12 . The process of  claim 1  wherein the mixture comprises a dispersed water phase and a continuous organic solvent phase.  
     
     
         13 . The process of  claim 1  wherein the mixture comprises an aqueous phase, a first organic solvent phase and a second organic solvent phase with the first and second organic solvents being immiscible.  
     
     
         14 . A process for the preparation of an oligomer, the process comprising 
 preparing a mixture containing (i) an enzyme, (ii) an α-hydroxy carboxylic acid and (iii) a peptide, the α-hydroxy carboxylic acid being present in the mixture as a free acid, acid halide, amide, ester or anhydride, and    forming an oligomer in the mixture, the oligomer containing a residue of the α-hydroxy carboxylic acid linked to peptide by an amide linkage.    
     
     
         15 . The process of  claim 14  wherein the α-hydroxy carboxylic acid is 2-hydroxy-4-(methylthio)butyric acid.  
     
     
         16 . The process of  claim 14  wherein the α-hydroxy carboxylic acid is 2-hydroxy-4-(methylthio)butyric acid and the peptide comprises methionine.  
     
     
         17 . The process of  claim 14  wherein the α-hydroxy carboxylic acid is 2-hydroxy-4-(methylthio)butyric acid and the peptide comprises the residues of at least two α-amino acids.  
     
     
         18 . The process of  claim 17  wherein the peptide comprises residues of methionine and lysine.  
     
     
         19 . The process of  claim 18  wherein the ratio of lysine to methionine residues contained in the peptide is about 3:1.  
     
     
         20 . The process of  claim 14  wherein the peptide comprises residues selected from one or more essential α-amino acids.  
     
     
         21 . The process of  claim 20  wherein the α-amino acid residues are selected from the group consisting of isoleucine, phenylalanine, leucine, lysine, methionine, threonine, tryptophan, histidine, and valine.  
     
     
         22 . The process of  claim 14  wherein the enzyme is a serine proteinase, thiol proteinases, metalloproteinase, acid proteinase, liver esterase, alkaline protease, or carbonic anhydrase, nonribosomal peptide synthetase, thrombin, cardosins A or B, or pronase.  
     
     
         23 . The process of  claim 14  wherein the enzyme is a protease selected from the group consisting of papain, subtilisin, thermolysin, α-chymotrypsin, and alkaline protease.  
     
     
         24 . The process of  claim 14  wherein the mixture is an aqueous solution.  
     
     
         25 . The process of  claim 14  wherein the mixture comprises an aqueous phase and an organic solvent phase.  
     
     
         26 . The process of  claim 14  wherein the mixture comprises a dispersed water phase and a continuous organic solvent phase.  
     
     
         27 . The process of  claim 14  wherein the mixture comprises an aqueous phase, a first organic solvent phase and a second organic solvent phase with the first and second organic solvents being immiscible.  
     
     
         28 . A process of providing an animal with its nutritional or pharmacological amino acid needs comprising providing the composition of  claim 24  to the animal wherein the method of administration is selected from the group consisting of oral administration, eye spray, placement in ear, placement in nasal cavity, and injection.  
     
     
         29 . The process of  claim 28  wherein the composition is orally administered to the animals.  
     
     
         30 . The process of  claim 29  wherein the animal is a ruminant.  
     
     
         31 . The process of  claim 30  wherein the ruminant is a dairy cow or beef cattle.  
     
     
         32 . The process of  claim 31  wherein the cow is a lactating dairy cow.