US2009227520A1PendingUtilityA1
Treatment methods using peptides related to amyloid precursor protein
Est. expiryApr 18, 2021(expired)· nominal 20-yr term from priority
Y02P20/55C07K 5/081C07K 14/4711A61K 38/06C07K 5/1013C07K 5/1019C07K 5/0817C07K 7/06A61P 25/28
42
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The invention provides a compound having formula X 1 -Arg-Xaa-Arg-X 2 in which X 1 and X 2 are up to 30 amino acid residues and Xaa is an amino acid residue. A preferred compound is the tripeptide Arg-Glu-Arg which corresponds to amino acid residues 328 to 330 of human amyloid precursor protein. The invention further provides a derivative of a polypeptide having the formula: X 1 -Arg-Xaa-Arg-X 2 wherein X 1 and X 2 , which may be the same or different, each represents from zero to 30 natural or synthetic amino acid residues or derivatives thereof and Xaa represents a natural or synthetic amino acid residue or derivative thereof, at least one functional group of at least one said amino acid residue or derivative thereof being protected by a protective group. The compounds of the invention are believed to be useful in the treatment of Alzheimer's disease and as cognitive enhancers.
Claims
exact text as granted — not AI-modified1 . A method of treatment
of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising: identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a compound effective to treat the neurodegenerative disease, the compound being at least one compound selected from the group of compounds having the following formulae:
Arg-Glu-Arg
(SEQ ID NO 9)
Arg-Glu-Arg-Met
(SEQ ID NO 10)
Met-Arg-Glu-Arg
(SEQ ID NO 11)
Arg-Glu-Arg-Met-Ser
(SEQ ID NO 3)
Ser-Met-Arg-Glu-Arg
(SEQ ID NO 4)
wherein each amino acid residue is independently in the D-form, or the L-form, or in the form of a salt thereof.
2 . A method according to claim 1 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
3 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a compound effective to produce the cognitive enhancement, the compound being at least one compound selected from the group of compounds having the following formulae:
Arg-Glu-Arg
(SEQ ID NO 9)
Arg-Glu-Arg-Met
(SEQ ID NO 10)
Met-Arg-Glu-Arg
(SEQ ID NO 11)
Arg-Glu-Arg-Met-Ser
(SEQ ID NO 3)
Ser-Met-Arg-Glu-Arg
(SEQ ID NO 4)
wherein each amino acid residue is independently in the D-form or the L-form, or in the form of a salt thereof.
4 . A method of treatment of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising:
identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a pharmaceutical composition effective to treat the neurodegenerative disease, the composition comprising at least one compound selected from the group of compounds having the following formulae:
Arg-Glu-Arg
(SEQ ID NO 9)
Arg-Glu-Arg-Met
(SEQ ID NO 10)
Met-Arg-Glu-Arg
(SEQ ID NO 11)
Arg-Glu-Arg-Met-Ser
(SEQ ID NO 3)
Ser-Met-Arg-Glu-Arg
(SEQ ID NO 4)
wherein each amino acid residue is independently in the D-form, or the L-form, or in the form of a salt thereof, and a pharmaceutically acceptable carrier, filler or excipient.
5 . A method according to claim 4 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
6 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a pharmaceutical composition effective to produce the cognitive enhancement, the composition comprising at least one compound selected from the group of compounds having the following formulae:
Arg-Glu-Arg
(SEQ ID NO 9)
Arg-Glu-Arg-Met
(SEQ ID NO 10)
Met-Arg-Glu-Arg
(SEQ ID NO 11)
Arg-Glu-Arg-Met-Ser
(SEQ ID NO 3)
Ser-Met-Arg-Glu-Arg
(SEQ ID NO 4)
wherein each amino acid residue is independently in the D-form or the L-form, or in the form of a salt thereof, and a pharmaceutically acceptable carrier, filler or excipient.
7 . A method of treatment of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising:
identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a pharmaceutical composition effective to treat the neurodegenerative disease, the composition comprising at least one compound selected from the group of compounds having the following formulae:
Arg-Glu-Arg
(SEQ ID NO 9)
Arg-Glu-Arg-Met
(SEQ ID NO 10)
Met-Arg-Glu-Arg
(SEQ ID NO 11)
Arg-Glu-Arg-Met-Ser
(SEQ ID NO 3)
Ser-Met-Arg-Glu-Arg
(SEQ ID NO 4)
wherein each amino acid residue is independently in the D-form, or the L-form, or in the form of a salt thereof, and said at least one compound is chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one compound.
8 . A method according to claim 7 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
9 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a pharmaceutical composition effective to produce the cognitive enhancement, the composition comprising at least one compound selected from the group of compounds having the following formulae:
Arg-Glu-Arg
(SEQ ID NO 9)
Arg-Glu-Arg-Met
(SEQ ID NO 10)
Met-Arg-Glu-Arg
(SEQ ID NO 11)
Arg-Glu-Arg-Met-Ser
(SEQ ID NO 3)
Ser-Met-Arg-Glu-Arg
(SEQ ID NO 4)
wherein each amino acid residue is independently in the D-form or the L-form, or in the form of a salt thereof, and said at least one compound is chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one compound.
10 . A method of treatment of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising
identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a compound effective to treat the neurodegenerative disease, the compound having the formula:
in which X 1 is a protective group and X 2 is H or a protective group.
11 . A method according to claim 10 , in which X 1 is an acyl group represented by the formula:
wherein R represents a substituted or unsubstituted straight- or branched-chain alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted straight or branched-chain aralkyl group or a substituted or unsubstituted aryl group.
12 . A method according to claim 11 , in which R represents a C 1 to C 6 straight- or branched-chain alkyl group.
13 . A method according to claim 12 , in which R represents a methyl group.
14 . A method according to claim 10 , in which X 2 is not H and at least one protective group is an aryl group represented by the formula:
wherein R represents a substituted or unsubstituted straight- or branched-chain alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted straight or branched-chain aralkyl group or a substituted or unsubstituted aryl group, the groups R being the same or different when two are present.
15 . A method according to claim 14 , in which R represents a C 1 to C 6 straight- or branched-chain alkyl group.
16 . A method according to claim 15 , in which R represents a methyl group.
17 . A method according to claim 10 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
18 . A method according to claim 10 , in which said at least one compound is administered in the form of a pharmaceutical composition comprising said at least one compound and a pharmaceutically acceptable carrier, filler or excipient.
19 . A method according to claim 10 , in which said at least one compound is chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one compound.
20 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a compound effective to produce the cognitive enhancement, the compound having the formula:
in which X 1 is a protective group and X 2 is H or a protective group.
21 . A method according to claim 20 , in which X 1 is an acyl group represented by the formula:
wherein R represents a substituted or unsubstituted straight- or branched-chain alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted straight or branched-chain aralkyl group or a substituted or unsubstituted aryl group.
22 . A method according to claim 21 , in which R represents a C 1 to C 6 straight- or branched-chain alkyl group.
23 . A method according to claim 22 , in which R represents a methyl group.
24 . A method according to claim 20 , in which X 2 is not H and at least one protective group is an aryl group represented by the formula:
wherein R represents a substituted or unsubstituted straight- or branched-chain alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted straight or branched-chain aralkyl group or a substituted or unsubstituted aryl group, the groups R being the same or different when two are present.
25 . A method according to claim 24 , in which R represents a C 1 to C 6 straight- or branched-chain alkyl group.
26 . A method according to claim 25 , in which R represents a methyl group.
27 . A method according to claim 20 , in which said at least one compound is administered in the form of a pharmaceutical composition comprising said at least one compound and a pharmaceutically acceptable carrier, filler or excipient.
28 . A method according to claim 20 , in which said at least one compound is chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one compound.
29 . A method of treatment of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising
identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a compound effective to treat the neurodegenerative disease, the compound having the formula:
30 . A method according to claim 24 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
31 . A method according to claim 30 , in which said at least one compound is administered in the form of a pharmaceutical composition comprising said at least one compound and a pharmaceutically acceptable carrier, filler or excipient.
32 . A method according to claim 30 , in which said at least one compound is chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one compound.
33 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a compound effective to produce the cognitive enhancement, the compound having the formula:
34 . A method according to claim 33 , in which said at least one compound is administered in the form of a pharmaceutical composition comprising said at least one compound and a pharmaceutically acceptable carrier, filler or excipient.
35 . A method according to claim 33 , in which said at least one compound is chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one compound.
36 . A method of treatment of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising
identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a peptide effective to treat the neurodegenerative disease, the peptide having the formula:
Arg-Glu-Arg
(SEQ ID NO 9)
wherein each amino acid residue is independently in the D-form or the L-form or in the form of a salt thereof, at least one functional group of the N-terminal arginine residue of said peptide being protected by at least one protective group.
37 . A method according to claim 36 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
38 . A method according to claim 36 , in which said N-terminal arginine residue of said peptide is protected by an acetyl group substituted for one of the hydrogen atoms of the N-terminal amino group of said N-terminal arginine residue.
39 . A method according to claim 38 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
40 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a peptide effective to produce the cognitive enhancement, the peptide having the formula:
Arg-Glu-Arg
(SEQ ID NO 9)
wherein each amino acid residue is independently in the D-form or the L-form or in the form of a salt thereof, at least one functional group of the N-terminal arginine residue of said peptide being protected by at least one protective group.
41 . A method according to claim 40 , in which said N-terminal arginine residue of said peptide is protected by an acetyl group substituted for one of the hydrogen atoms of the N-terminal amino group of said N-terminal arginine residue.
42 . A method of treatment of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising
identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a pharmaceutical composition effective to treat the neurodegenerative disease, the pharmaceutical composition comprising a peptide having the formula:
Arg-Glu-Arg
(SEQ ID NO 9)
wherein each amino acid residue is independently in the D-form or the L-form or in the form of a salt thereof, at least one functional group of the N-terminal arginine residue of said peptide being protected by at least one protective group, and a pharmaceutically acceptable carrier, filler or excipient.
43 . A method according to claim 42 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
44 . A method according to claim 42 , in which said N-terminal arginine residue of said peptide is protected by an acetyl group substituted for one of the hydrogen atoms of the N-terminal amino group of said N-terminal arginine residue.
45 . A method according to claim 44 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
46 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a pharmaceutical composition effective to produce the cognitive enhancement, the pharmaceutical composition comprising a peptide having the formula:
Arg-Glu-Arg
(SEQ ID NO 9)
wherein each amino acid residue is independently in the D-form or the L-form or in the form of a salt thereof, at least one functional group of the N-terminal arginine residue of said peptide being protected by at least one protective group, and a pharmaceutically acceptable carrier, filler or excipient.
47 . A method according to claim 46 , in which said N-terminal arginine residue of said peptide is protected by an acetyl group substituted for one of the hydrogen atoms of the N-terminal amino group of said N-terminal arginine residue.
48 . A method of treatment of a neurodegenerative disease in an animal, said disease being characterised by loss of memory or loss of cognitive function, comprising
identifying an animal suffering or potentially suffering from a neurodegenerative disease; and administering to the animal an amount of a pharmaceutical composition effective to treat the neurodegenerative disease, the pharmaceutical composition comprising a peptide having the formula:
Arg-Glu-Arg
(SEQ ID NO 9)
wherein each amino acid residue is independently in the D-form or the L-form or in the form of a salt thereof, at least one functional group of the N-terminal arginine residue of said peptide being protected by at least one protective group and said peptide being chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one peptide.
49 . A method according to claim 48 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
50 . A method according to claim 48 , in which said N-terminal arginine residue of said peptide is protected by an acetyl group substituted for one of the hydrogen atoms of the N-terminal amino group of said N-terminal arginine residue.
51 . A method according to claim 50 , in which the animal is a human and the neurodegenerative disease is Alzheimer's disease.
52 . A method of producing a cognitive enhancement effect in an animal, comprising
providing an animal in which the effect is to be produced; and administering to the animal an amount of a pharmaceutical composition effective to produce the cognitive enhancement, the pharmaceutical composition comprising a compound having the formula:
Arg-Glu-Arg
(SEQ ID NO 9)
wherein each amino acid residue is independently in the D-form or the L-form or in the form of a salt thereof, at least one functional group of the N-terminal arginine residue of said peptide being protected by at least one protective group and said peptide being chemically or physically linked to a further molecule or vehicle for pharmaceutical delivery of said at least one compound.
53 . A method according to claim 52 , in which said N-terminal arginine residue of said peptide is protected by an acetyl group substituted for one of the hydrogen atoms of the N-terminal amino group of said N-terminal arginine residue.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.