Synthetic analogues of neural regeneration peptides

Abstract

Embodiments of this invention include synthetic compounds (NRP analogues) of peptides termed neural regeneration peptides (NRPs). NRP analogues are made by substituting amino acids in the native peptide sequence, modifying amino acids chemically, by replacing amino acids with synthetic moieties, by stabilizing β-turns, acetylation of terminal glycine residues or by cyclization. NRP analogues can be used to treat a variety of conditions involving degeneration of neural cells, and includes treating disorders of the nervous system, including peripheral neuropathy, multiple sclerosis, diabetic peripheral neuropathy, neurotoxin-induced neurodegeneration, and amyotrophic lateral sclerosis.

1 . A neural regeneration peptide (NRP) compound selected from the group comprising the sequence selected from the group consisting of 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 and SEQ ID NO:11. 
     
     
         2 . The NRP compound of  claim 1  where the NRP compound is selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:5. 
     
     
         3 . The NRP compound of  claim 1  where the NRP compound is SEQ ID NO:6. 
     
     
         4 . The NRP compound of  claim 1  where the NRP compound is SEQ ID NO:7. 
     
     
         5 . The NRP compound of  claim 1  where the NRP compound is and SEQ ID NO:8. 
     
     
         6 . The NRP compound of  claim 1  where the NRP compound is selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11. 
     
     
         7 . A pharmaceutical composition comprising a NRP compound of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         8 . A method of treating a neurological disorder characterized by loss of cells in an animal, comprising administering to said animal a pharmaceutically effective amount of NRP compound of  claim 1  or a pharmaceutical composition as above. 
     
     
         9 . The method of  claim 8 , wherein said NRP compound consists of the sequence SEQ ID NO:4 or SEQ ID NO:5. 
     
     
         10 . The method of  claim 8 , wherein said NRP compound consists of the sequence SEQ ID NO:6. 
     
     
         11 . The method of  claim 8 , wherein said NRP compound consists of the sequence SEQ ID NO:7. 
     
     
         12 . The method of  claim 8 , wherein said NRP compound consists of the sequence SEQ ID NO:8. 
     
     
         13 . The method of  claim 8 , wherein said NRP compound consists of the sequence SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11. 
     
     
         14 . The method of  claim 8 , wherein said disorder is of neural cells. 
     
     
         15 . The method of  claim 8 , wherein said neurological disorder is amyotrophic lateral sclerosis, neurotoxin injury, oxidative injury, multiple sclerosis, peripheral neuropathy, hypoxia/ischemia, traumatic brain injury, or coronary artery bypass graft surgery. 
     
     
         16 . The method of  claim 8 , where said neurological disorder is diabetic peripheral neuropathy. 
     
     
         17 . A synthetic NRP compound, wherein said compound is produced from a NRP by modifying a β-turn, a peptide domain APGR, a peptide domain RAGG, a replacement of a glycine residue with asparagine, replacement of an L-amino acid by a D-amino acid, or cyclization of said NRP. 
     
     
         18 . A method of treating a neurological disorder characterized by neurodegeneration, comprising administering to a patient in need thereof, a synthetic NRP compound of  claim 17 .