Neuroprotection using NAP-like and SAL-like peptide mimetics
View Patent ↗This invention relates to NAP-like and SAL-like peptide mimetics, polypeptides, or small molecules derived from them, and their use in the treatment of neuronal dysfunction, neurodegenerative disorders cognitive deficits, neuropsychiatric disorders, and autoimmune disease.
1. A peptide mimetic consisting of the amino acid sequence of formula
(R 1 ) a —(R 2 )—(R 3 ) b
wherein:
R 1 is an amino acid sequence cosisting of 1 to 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs;
R 2 is NATLSIHQ (SEO ID NO:4);
R 3 is an amino acid sequence consisting of 1 to 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs;
a and b are independently selected and are equal to zero or one;
wherein none or as many as all of the amino acids in the peptide mimetic are in the D configuration; and
with the proviso that the peptide mimetic does not comprise the sequence NAPVSIPQ (SEQ ID NO:1) or SALLRSIPA (SEQ ID NO:19).
2. The peptide mimetic of claim 1 , wherein at least one amino acid of R 2 is a D-amino acid.
3. The peptide mimetic of claim 1 , wherein each amino acid of R 2 is a D-amino acid.
4. A peptide mimetic consisting of the amino sequence of formula
(R 1 ) a —(R 2 )—(R 3 ) b
and at least one protecting group,
wherein:
R 1 is an amino acid sequence consisting of 1 to 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs;
R 2 is NATLSIHQ (SEQ ID NO:4);
R 3 is an amino acid sequence consisting of 1 to 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs;
a and b are independently selected and are equal to zero or one;
wherein none or as many as all of the amino acids in the peptide mimetic are in the D configuration; and
with the proviso that the peptide mimetic does not comprise the sequence NAPVSIPQ (SEQ ID NO:1) or SALLRSIPA (SEQ ID NO: 19).
5. The peptide mimetic of claim 1 , wherein the peptide mimetic is NATLSIHQ (SEQ ID NO:4).
6. The peptide mimetic of claim 5 , wherein at least one amino acid is a D-amino acid.
7. The peptide mimetic of claim 5 , wherein each amino acid is a D-amino acid.
8. A peptide mimetic consisting of the amino acid sequence NATLSIHQ (SEQ ID NO:4) and at least one protecting group.
9. A pharmaceutical composition comprising the peptide mimetic of claim 1 .
10. The pharmaceutical composition of claim 9 , further comprising a neuroprotective polypeptide comprising an amino acid sequence selected from the group consisting of NAPVSIPQ (SEQ ID NO:1) and SALLRSIPA (SEQ ID NO:19).