Casein Derived Peptides And Uses Thereof

Abstract

Biologically active peptides that are derived from or are similar to sequences identical with the N-terminus of the αS1 fraction of milk casein. These peptides are capable of stimulating and enhancing immune response, protecting against viral infection, normalizing serum cholesterol levels, and stimulating hematopoiesis. The casein-derived peptides are non-toxic and can be used to treat and prevent immune pathologies, hypercholesterolemia, hematological disorders and viral-related diseases, alone or in combination with other peptides or blood cell stimulating factors.

1 . A method of treating or preventing infectious disease or condition is selected from the group consisting of a viral disease, a viral infection, AIDS, and infection by HIV, the method comprising administering to a subject in need thereof a therapeutically effective amount of a peptide derived from the N terminus portion of alpha-S1 casein. 
     
     
         2 . The method of  claim 1 , wherein said peptide is a fragment derived from the N terminus portion of alpha-S1 casein by fragmentation of alpha-S1 casein. 
     
     
         3 . The method of  claim 1 , wherein said peptide derived from the N terminus portion of alpha-S1 casein is a synthetic peptide. 
     
     
         4 . The method of  claim 1 , wherein said peptide derived from the N terminus portion of alpha-S1 casein has a sequence as set forth in one of SEQ ID NOs: 1-25. 
     
     
         5 . The method of  claim 1 , wherein said peptide derived from the N terminus portion of alpha-S1 casein is a peptide derived from natural casein, in combination with peptides derived from natural non-alpha-S1 casein. 
     
     
         6 . The method of  claim 5 , wherein said peptide derived from natural casein, in combination with peptides derived from natural non-alpha-S1 casein, is prepared according to a preparation method comprising proteolytic digestion of said natural casein in solution to form a digested material solution; and centrifugation of said digested material solution to obtain said caseicidin peptide preparation derived from natural casein. 
     
     
         7 . The method of  claim 6 , wherein said preparation method further comprises a method of low-temperature processing of casein, the method comprising: a) obtaining a casein proteolytic hydrolysate; to form said caseicidin peptide preparation derived from natural casein. 
     
     
         8 . The method of  claim 7 , wherein said casein proteolytic hydrolysate is prepared with proteolytic enzymes, the method further comprising b) cooling said casein proteolytic hydrolysate so as to inactivate said proteolytic enzymes; c) adjusting the pH of said casein protein hydrolysate to an acid pH; d) centrifuging said acidic casein protein hydrolysate, collecting the supernatant, filtering said supernatant and further acidifying said supernatant so as to precipitate proteins derived from natural casein; e) separating and collecting said precipitate; f) adjusting the pH of said precipitate to an alkaline pH so as to irreversibly inactivate said proteolytic enzymes; and g) adjusting the pH of said precipitate to below pH 9. 
     
     
         9 . The method of  claim 8 , wherein further acidifying said filtrate of stage d comprises adding acid to about at least 10% (v/v) acid. 
     
     
         10 . The method of  claim 8 , wherein said adjusting said pH of stage f comprises increasing a pH of said precipitate to pH 9-13. 
     
     
         11 . A method for preventing onset of disease symptoms or to reduce severity of disease symptoms and/or for treating HIV or AIDS, the method comprising administering to a subject in need thereof a therapeutically effective amount of a peptide derived from the N terminus portion of alpha-S1 casein as an adjunct therapy. 
     
     
         12 . The method of  claim 11 , wherein said peptide is a fragment derived from the N terminus portion of alpha-S1 casein by fragmentation of alpha-S1 casein. 
     
     
         13 . The method of  claim 11 , wherein said peptide derived from the N terminus portion of alpha-S1 casein is a synthetic peptide. 
     
     
         14 . The method of  claim 11 , wherein said peptide derived from the N terminus portion of alpha-S1 casein has a sequence as set forth in one of SEQ ID NOs: 1-25. 
     
     
         15 . The method of  claim 11 , wherein said peptide derived from the N terminus portion of alpha-S1 casein is a peptide derived from natural casein, in combination with peptides derived from natural non-alpha-S1 casein. 
     
     
         16 . The method of  claim 15 , wherein said peptide derived from natural casein, in combination with peptides derived from natural non-alpha-S1 casein, is prepared according to a preparation method comprising proteolytic digestion of said natural casein in solution to form a digested material solution; and centrifugation of said digested material solution to obtain said caseicidin peptide preparation derived from natural casein. 
     
     
         17 . The method of  claim 16 , wherein said preparation method further comprises a method of low-temperature processing of casein, the method comprising: a) obtaining a casein proteolytic hydrolysate; to form said caseicidin peptide preparation derived from natural casein. 
     
     
         18 . The method of  claim 17 , wherein said casein proteolytic hydrolysate is prepared with proteolytic enzymes, the method further comprising b) cooling said casein proteolytic hydrolysate so as to inactivate said proteolytic enzymes; c) adjusting the pH of said casein protein hydrolysate to an acid pH; d) centrifuging said acidic casein protein hydrolysate, collecting the supernatant, filtering said supernatant and further acidifying said supernatant so as to precipitate proteins derived from natural casein; e) separating and collecting said precipitate; f) adjusting the pH of said precipitate to an alkaline pH so as to irreversibly inactivate said proteolytic enzymes; and g) adjusting the pH of said precipitate to below pH 9. 
     
     
         19 . The method of  claim 18 , wherein further acidifying said filtrate of stage d comprises adding acid to about at least 10% (v/v) acid. 
     
     
         20 . The method of  claim 18 , wherein said adjusting said pH of stage f comprises increasing a pH of said precipitate to pH 9-13. 
     
     
         21 . The method of  claim 11 , further comprising reducing viral load.