Synthesis, modification and reduction of primary structure of hypotensive peptides present in scorpion venom for optimizing their use as a hypotensive medicament

Abstract

The present invention relates to synthetic and recombinant peptide primary structures including an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 12, wherein the primary structure includes an +aa-Pro-Pro amino acid in which “+aa” is Lys, Arg, His or a modified amino acid having a positive charge at physiological pH. The present invention also relates to a pharmaceutical composition including at least one peptide having a primary structure as defined above.

1 . A peptide comprising at least one member selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11 SEQ ID NO:12, and analogs thereof, wherein each of the analogs has a primary structure identical to one of SEQ ID NOs: 1-12 with a substitute amino acid substituted for a lysine closest to a carboxy-terminus of the peptide, said substitute amino acid having a positive charge at physiological pH.  
     
     
         2 . The peptide of  claim 1 , wherein the peptide possesses anti-hypertensive activity.  
     
     
         3 . The peptide of  claim 1 , containing less than 24 amino acids.  
     
     
         4 . The peptide of  claim 1 , consisting of one member of the group.  
     
     
         5 . The peptide of  claim 1 , wherein the peptide is synthetic.  
     
     
         6 . The peptide of  claim 1 , wherein the peptide is recombinant.  
     
     
         7 . A pharmaceutical composition comprising at least one peptide of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide is present in the composition in an anti-hypertensive amount.  
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide contains less than 24 amino acids.  
     
     
         10 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide consists of one member of the group.  
     
     
         11 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide is synthetic.  
     
     
         12 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide is recombinant.  
     
     
         13 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide comprises SEQ ID NO: 1.  
     
     
         14 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide comprises SEQ ID NO: 5.  
     
     
         15 . The pharmaceutical composition of  claim 7 , wherein the at least one peptide comprises SEQ ID NO: 6.  
     
     
         16 . A method for treating hypertension, comprising administering to an animal an anti-hypertensive amount of at least one peptide of  claim 1.