Synthetic analogues of neural regeneration peptides
AssigneeCuronz Holdings Company Limited
InventorsPaul William Richard Harris, Margaret Anne Brimble, Frank Sieg
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Abstract
Embodiments of this invention include synthetic compounds (NRP analogs) of peptides termed neural regeneration peptides (NRPs). NRP analogs 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 analogs 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.
Claims7
A synthetic neural regeneration peptide (NRP) compound, wherein said compound is produced from a NRP comprising the amino acid sequence of SEQ ID NO:1 (GRRAAPGRAGG) by:
- (i) modifying a β-turn in said sequence by:
- (a) modifying a peptide domain APGR (SEQ ID NO:2) in said sequence, by substituting an aminoisobutyric acid (Aib) residue for an alanine and/or glycine residue in the peptide domain APGR (SEQ ID NO:2), or
- (b) modifying a peptide domain RAGG (SEQ ID NO:3) in said sequence, by substituting an aminoisobutyric acid (Aib) residue for an alanine and/or glycine residue in the peptide domain RAGG (SEQ ID NO:3),
- (ii) replacing an L-arginine residue with a D-arginine residue in said sequence, or
- (iii) cyclization of said sequence by:
- (iii)(a) adding a cysteine residue to each end of said sequence and oxidizing the resulting cysteine-augmented product,
- (iii)(b) replacing each of the N-terminal and C-terminal residues of said sequence with a cysteine and oxidizing the resulting cysteine-substituted product, or
- (iii)(c) creating an amide bond between the N-terminal and C-terminal residues of said sequence, and
- (iv) optionally, amidating the C-terminal residue in said sequence, or amidating the compound of any one of (i)-(iii).
Dependencies are inferred from the claim text.