Pharmaceutical lysine-containing polypeptide compositions and methods of use thereof

Abstract

Pharmaceutical compositions and methods are provided for the therapy of immunodeficient, immunodepressed or hyperactive immune states and for the prevention and treatment of opportunistic infections in such states comprising administering to a subject a pharmaceutically acceptable composition comprising as an active ingredient peptides having the formula R′-L-Glx-L-Glx-L-Lys-R″ and/or their pharmaceutically acceptable salts; wherein Glx is Gln or Glu.

What is claimed is:  
     
         1 . A composition comprising a peptide having the formula R′-Glx-Glx-Lys-R″ or a pharmaceutically acceptable salt thereof; 
 wherein Glx is Glu or Gln; R′ is H- or a first amino acid sequence having fewer than 7 amino acids; R″ is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 5 and not more than 9 amino acids.  
 
     
     
         2 . The composition of  claim 1 , wherein V is H-, Thr-Ala-, Thr-Pro-, Ser-Ala-, Ser-Pro-, Ser-Ser-, Met-Leu-Thr-Ala-, or Leu-Thr-Ala-; and R″ is -H, -Ala, -Ala-Ala or -Ala-Vat.  
     
     
         3 . A composition of  claim 2 , wherein the peptide is L-Thr-L-Pra-L-Glu-L-Glu-L-Lys.  
     
     
         4 . A composition of  claim 2 , wherein the peptide is L-Thr-L-Ala-L-Glu-L-Glu-L-Lys.  
     
     
         5 . A pharmaceutical preparation comprising: 
 a peptide having the formula R′-Glx-Lys-R″ or a pharmaceutically acceptable salt thereof, wherein Glx is Glu or Gln; R′ is H- or a first amino acid sequence having fewer than 7 amino acids; R″ is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 2 and not more than 9 amino acids; and    a physiologically acceptable carrier.    
     
     
         6 . The pharmaceutical preparation of  claim 5 , wherein V is H-, Glx-, Thr-Ala-Glx-, Thr-Pro-Glx-, Ser-Ala-Glx-, Ser-Pro-Glx-, Ser-Ser-Glx-, Met-Leu-Thr-Ala-Glx-, or Leu-Thr-Ala-Glx-; and R″ is -H, -Ala, -Ala-Ala or -Ala-Val.  
     
     
         7 . The pharmaceutical preparation of  claim 6 , wherein the peptide is L-Glu-L-Lys.  
     
     
         8 . The pharmaceutical preparation of  claim 6 , wherein the peptide is L-Thr-L-Pro-L-Glu-L-Glu-L-Lys.  
     
     
         9 . A composition of  claim 6 , wherein the peptide is L-Thr-L-Ala-L-Glu-L-Glu-L-Lys.  
     
     
         10 . A method for modulating the activity of a host's immune system, comprising administering to the host a peptide having the formula R′-Glx-Lys-R″ or a pharmaceutically acceptable salt thereof, wherein Glx is Glu or Gln; R′ is H-or a first amino acid sequence having fewer than 7 amino acids; R″ is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 2 and not more than 9 amino acids.  
     
     
         11 . A method as in  claim 10 , wherein R′ is H-, Glx-Thr-Ala-Glx-, Thr-Pro-Glx-, Ser-Ala-Gix-, Ser-Pro-Glx-, Ser-Ser-Glx-, Met-Leu-Thr-Ala-Glx-, or Leu-Thr-Ala-Glx-; and R″ is -H, -Ala, -Ala-Ala or -Ala-Val.  
     
     
         12 . A method as in  claim 11 , wherein the peptide is L-Thr-L-Ala-L-Glu-L-Glu-L-Lys or L-Glu-L-Lys.  
     
     
         13 . A method as in  claim 10 , wherein the peptide is administered in a physiologically acceptable carrier.  
     
     
         14 . A method for treating an infection in a host, comprising administering to the host a peptide having the formula R′-Glx-Lys-R″ or a pharmaceutically acceptable salt thereof, wherein Glx is Glu or Gln; V is H- or a first amino acid sequence having fewer than 7 amino acids; R″ is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 2 and not mare than 9 amino acids.  
     
     
         15 . The method as in  claim 14 , wherein R′ is H-, Glx-, Thr-Ala-Glx-, Thr-Pro-Glx-, Ser-Ala-Glx-, Ser-Pro-Glx-, Ser-Ser-Glx-; Met-Leu-Thr-Ala-Glx-, or Leu-Thr-Ala-Glx-; and R″ is -H, -Ala, -Ala-Ala or -Ala-Val.  
     
     
         16 . The method as in  claim 14 , wherein the peptide is L-Thr-L-Ala-L-Glu-L-Glu-L-Lys or L-Glu-L-Lys.  
     
     
         17 . The method as in  claim 14 , wherein the infection is a bacterial infection.  
     
     
         18 . The method as in  claim 17 , further comprising administering an antibiotic to the host.  
     
     
         19 . The method as in  claim 14 , wherein the infection is a viral infection.  
     
     
         20 . The method as in  claim 19 , further comprising administering an anti-viral agent to the host.  
     
     
         21 . The method as in  claim 14 , wherein the infection is a fungal infection.  
     
     
         22 . The method as in  claim 21 , further comprising administering an anti-fungal agent to the host.  
     
     
         23 . The method as in  claim 14 , wherein the infection is a parasitic infection.  
     
     
         24 . The method as in  claim 23 , further comprising administering an anti-parasitic agent to the host.  
     
     
         25 . The method as in  claim 14 , wherein the peptide is administered intravenously, intramuscularly, intrathecally, subcutaneously, intraperitoneally, intranasally, orally, intrabronchially, rectally, or topically.  
     
     
         26 . A method for treating atopic states in a host comprising administering to the host a peptide having the formula R′-Glx-Lys-R″ or a pharmaceutically acceptable salt thereof, wherein Glx is Glu or Gin; TV is H- or a first amino acid sequence having fewer than 7 amino acids; R″ is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 2 and not more than 9 amino acids.  
     
     
         27 . The method as in  claim 26 , wherein R′ is H-, Glx-, Thr-Ala-Glx-, Thr-Pro-Glx-, Ser-Ala-Glx-, Ser-Pro-Glx-, Ser-Ser-Glx-, Met-Leu-Thr-Ala-Glx-, or Leu-Thr-Ala-Glx-; and R″ is -H, -Ala, -Ala-Ala or -Ala-Val.  
     
     
         28 . The method as in  claim 27 , wherein the peptide is L-Thr-L-Ala-L-Glu-L-Glu-L-Lys or L-Glu-L-Lys.  
     
     
         29 . A method of treating leukocytic disorders in a host comprising administering to the host a peptide having the formula R′-Glx-Lys-R″ or a pharmaceutically acceptable salt thereof, wherein Glx is Glu or Gln; TV is H- or a first amino acid sequence having fewer than 7 amino acids; R″ is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 2 and not more than 9 amino acids.  
     
     
         30 . A method for augmenting vaccinations in a host comprising administering to the host a peptide having the formula R′-Glx-Lys-R″ or a pharmaceutically acceptable salt thereof, wherein Glx is Glu or Gln; R′ is H- or a first amino acid sequence having fewer than 7 amino acids; R″ is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 2 and not more than 9 amino acids.