Synthetic peptides derived from vitronectin and pharmaceutical compositions comprising them
AssigneeYeda Research and Development Co. Ltd.
InventorShmuel Shaltiel
Life of this patent
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Abstract
The invention relates to synthetic peptides derived from the K.sup.348 -A.sup.380 (8-40 of SEQ ID NO:1) sequence of the vitronectin molecule. The peptides modulate the biological activities of plasminogen activator inhibitor-1 (PAI-1) and are useful as active ingredients of pharmaceutical compositions for the treatment of disorders such as bleeding disorders, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, tumor cell invasion and metastasis, inflammation, liver diseases, bacterial blood infections, pregnancy toxicosis, and pathological conditions associated with the control of angiogenesis, or with nerve regeneration, or with excessive tPA-mediated proteolysis.
Claims19
A molecule capable of inhibiting a biological activity of plasminogen activator inhibitor-1 (PAI-1) consisting of a peptide having 8 to 23 consecutive amino acids of the sequence Lys-Lys-Glu-Arg-Phe-Arg-His-Arg-Asn-Arg-Lys-Gly-Tyr-Arg-Ser-Gln-Arg-Gly-Hi s-Ser-Arg-Gly-Arg (8-30 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide, wherein said molecule does not include the peptides of residues 8-21 of SEQ ID NO:1 or 17-30 of SEQ ID NO:1.
A method of treating an animal in need of increased fibrinolysis, comprising administering an effective amount of a molecule capable of inhibiting a biological activity of plasminogen activator inhibitor-1 (PAI-1) consisting of a peptide having 8 to 23 consecutive amino acids of the sequence Lys-Lys-Gln-Arg-Phe-Arg-His-Arg-Asn-Arg-Lys-Gly-Tyr-Arg-Ser-Gln-Arg-Gly-Hi s-Ser-Arg-Gly-Arg (8-30 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide.
A molecule capable of enhancing a biological activity of plasminogen activator inhibitor-1 (PAI-1), consisting of a peptide having 7 to 19 consecutive amino acids of the sequence:
- Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg-Asn-Gln-Asn-Ser-Arg-Arg-Pro-Ser-Arg-Ala (22-40 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide, wherein said molecule of the peptide does not include the peptide of residues 26-39 of SEQ ID NO:1.
A method for the treatment of disorders associated with excessive fibrinolysis, comprising administering an effective amount of a molecule capable of enhancing a biological activity of plasminogen activator inhibitor-1 (PAI-1), consisting of a peptide having 7 to 19 consecutive amino acids of the sequence:
- Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg-Asn-Gln-Asn-Ser-Arg-Arg-Pro-Ser-Arg-Ala (22-40 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide.
Dependencies are inferred from the claim text.