Anticoagulant peptide fragments derived from apolipoprotein B-100
AssigneeUniversity College London
InventorsKarl Richard Bruckdorfer, Camille Ettelaie
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Abstract
The present invention provides a peptide compound of formula Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1) where: X1 represents S or Y, X2 represents T or I, Z1 represents the N terminus of the peptide, or from 1 to 47 amino acids, Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 77 amino acids; or a variant of this peptide which contains one or more internal deletions, insertions or substitutions and which substantially retains anti-coagulant properties of apoB-100.
Claims48
A peptide whose amino acid sequence is
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 47 amino acids, and
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 77 amino acids;
- or a peptide whose sequence differs from the sequence of the peptide of SEQ ID NO:1 by up to 15% by virtue of internal deletions, insertions or substitutions;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- with the proviso that the sequence of said peptide is not the sequence of amino acids 3120-3159 of apoB-100.
A peptide whose amino acid sequence is
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 47 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 77 amino acids;
- or a peptide whose sequence differs from the sequence of the peptide of SEQ ID NO:1 by up to 15% by virtue of internal deletions, insertions or substitutions;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- wherein, when X1 is Y and X2 is I, Z1 represents 20 or less amino acids.
A peptide comprising the amino acid sequence
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- Z1—Q—X1—K—K—N—K—H—R—Z2 (SEQ ID NO:2)
- Z1—A—Q—X1—K—K—N—K—H—Z2 (SEQ ID NO:3)
- Z1—A—Q—X1—K—K—N—K—H—R—Z2 (SEQ ID NO:4)
- Z1—Q—X1—K—K—N—K—H—R—H—Z2 (SEQ ID NO:5)
- Z1—A—Q—X1—K—K—N—K—H—R—H—Z2 (SEQ ID NO:6)
- Z1—Q—X1—K—K—N—K—H—R—H—S—Z2 (SEQ ID NO:7)
- Z1—A—Q—X1—K—K—N—K—H—R—H—S—Z2 (SEQ ID NO:8)
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—Z2 (SEQ ID NO:9)
- Z1—A—Q—X1—K—K—N—K—H—R—H—S—X2—Z2 (SEQ ID NO:10)
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—Z2 (SEQ ID NO:11)
- or a sequence of any one of SEQ ID Nos. 1 to 11 comprising up to 4 amino acid substitutions;
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 20 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 20 amino acids;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100).
A peptide comprising the amino acid sequence
- Z1KKNKZ2;
- where:
- Z1 represents the N terminus of the peptide, or from 1 to 20 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 20 amino acids;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100).
A peptide whose amino acid sequence is
- K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I.
A peptide whose amino acid sequence is the sequence of amino acids 21 to 118 of SEQ ID NO:12.
A pharmaceutical composition comprising a peptide whose amino acid sequence is
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 47 amino acids, and
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 77 amino acids;
- or a peptide whose sequence differs from the sequence of the peptide of SEQ ID NO:1 by up to 15% by virtue of internal deletions, insertions or substitutions;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- with the proviso that the sequence of said peptide is not the sequence of amino acids 3120-3159 of apoB-100;
- and a pharmaceutically acceptable diluent or carrier.
A pharmaceutical composition a peptide whose amino acid sequence is
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 47 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 77 amino acids;
- or a peptide whose sequence differs from the sequence of the peptide of SEQ ID NO:1 by up to 15% by virtue of internal deletions, insertions or substitutions;
- comprising said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- wherein, when X1 is Y and X2 is I, Z1 represents 20 or less amino acids;
- and a pharmaceutically acceptable diluent or carrier.
A pharmaceutical composition comprising a peptide comprising the amino acid sequence
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- Z1—Q—X1—K—K—N—K—H—R—Z2 (SEQ ID NO:2)
- Z1—A—Q—X1—K—K—N—K—H—Z2 (SEQ ID NO:3)
- Z1—A—Q—X1—K—K—N—K—H—Z2 (SEQ ID NO:4)
- Z1—Q—X1—K—K—N—K—H—R—H—Z2 (SEQ ID NO:5)
- Z1—A—Q—X1—K—K—N—K—H—R—H—Z2 (SEQ ID NO:6)
- Z1—Q—X1—K—K—N—K—H—R—H—S—Z2 (SEQ ID NO:7)
- Z1—A—Q—X1—K—K—N—K—H—R—H—S—Z2 (SEQ ID NO:8)
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—Z2 (SEQ ID NO:9)
- Z1—A—Q—X1—K—K—N—K—H—R—H—S—X2—Z2 (SEQ ID NO:10)
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—Z2 (SEQ ID NO:11)
- or a sequence of any one of SEQ ID Nos. 1 to 11 comprising up to 4 amino acid substitutions;
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 20 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 20 amino acids;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- and a pharmaceutically acceptable diluent or carrier.
A pharmaceutical composition comprising a peptide comprising the amino acid sequence Z1KKNKZ2;
- where:
- Z1 represents the N terminus of the peptide, or from 1 to 20 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 20 amino acids;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- and a pharmaceutically acceptable diluent or carrier.
A pharmaceutical composition comprising a peptide whose amino acid sequence is
- K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I;
- and a pharmaceutically acceptable diluent or carrier.
A pharmaceutical composition comprising a peptide whose amino acid sequence is the sequence of amino acids 21 to 118 of SEQ ID NO:12;
- and a pharmaceutically acceptable diluent or carrier.
A method of treatment of a patient who requires therapy for a condition requiring inhibition of a thromboplastin-related process which comprises administering to said patient an effective amount of a peptide whose amino acid sequence is
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 47 amino acids, and
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 77 amino acids;
- or a peptide whose sequence differs from the sequence of the peptide of SEQ ID NO:1 by up to 15% by virtue of internal deletions, insertions or substitutions;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- with the proviso that the sequence of said peptide is not the sequence of amino acids 3120-3159 of apoB-100.
A method of treatment of a patient who requires therapy for a condition requiring inhibition of a thromboplastin-related process which comprises administering to said patient an effective amount of a peptide whose amino acid sequence is
- Z1—K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T—Z2 (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 47 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 77 amino acids;
- or a peptide whose sequence differs from the sequence of the peptide of SEQ ID NO:1 by up to 15% by virtue of internal deletions, insertions or substitutions;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100);
- wherein, when X1 is Y and X2is I, Z1 represents 20 or less amino acids.
A method of treatment of a patient who requires therapy for a condition requiring inhibition of a thromboplastin-related process which comprises administering to said patient an effective amount of a peptide comprising the amino acid sequence
- Z1-K-A-Q-X1-K-K-N-K-H-R-H-S-X2-T-Z2 (SEQ ID NO:1) Z1-Q-X1-K-K-N-K-H-R-Z2 (SEQ ID NO:2) Z1-A-Q-X1-K-K-N-K-H-Z2 (SEQ ID NO:3) Z1-A-Q-X1-K-K-N-K-H-R-Z2 (SEQ ID NO:4) Z1-Q-X1-K-K-N-K-H-R-H-Z2 (SEQ ID NO:5) Z1-A-Q-X1-K-K-N-K-H-R-H-Z2 (SEQ ID NO:6) Z1-Q-X1-K-K-N-K-H-R-H-S-Z2 (SEQ ID NO:7) Z1-A-Q-X1-K-K-N-K-H-R-H-S-Z2 (SEQ ID NO:8) Z1-K-A-Q-X1-K-K-N-K-H-R-H-S-Z2 (SEQ ID NO:9) Z1-A-Q-X1-K-K-N-K-H-R-H-S-X2-Z2 (SEQ ID NO:10) Z1-K-A-Q-X1-K-K-N-K-H-R-H-S-X2-Z2 (SEQ ID NO:11)
- or a sequence of any one of SEQ ID NOs. 1 to 11 comprising up to 4 amino acid substitutions;
- where:
- X1 represents S or Y,
- X2 represents T or I,
- Z1 represents the N terminus of the peptide, or from 1 to 20 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 20 amino acids;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100).
A method of treatment of a patient who requires therapy for a condition requiring inhibition of a thromboplastin-related process which comprises administering to said patient an effective amount of a peptide comprising the amino acid sequence Z1KKNKZ2;
- where:
- Z1 represents the N terminus of the peptide, or from 1 to 20 amino acids,
- Z2 represents the C terminus of the peptide, a terminal amide group, or from 1 to 20 amino acids;
- said peptide possessing 0.5 fold or more the anti-coagulant activity of apolipoprotein B-100 (apoB-100).
A method of treatment of a patient who requires therapy for a condition requiring inhibition of a thromboplastin-related process which comprises administering to said patient an effective amount of a peptide whose amino acid sequence is
- K—A—Q—X1—K—K—N—K—H—R—H—S—X2—T (SEQ ID NO:1)
- where:
- X1 represents S or Y,
- X2 represents T or I.
A method of treatment of a patient who requires therapy for a condition requiring inhibition of a thromboplastin-related process which comprises administering to said patient an effective amount of a peptide whose amino acid sequence is the sequence of amino acids 21 to 118 of SEQ ID NO:12.
Dependencies are inferred from the claim text.