Novel antioxidant, nucleic acid constructs encoding same, pharmaceutical compositions containing same and use of same for reducing oxidative-stress
AssigneeRappaport Family Institute for Research in the Medical Sciences
InventorAndrew P. Levy
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Abstract
Novel haptoglobin derived antioxidants, nucleic acid constructs encoding same, pharmaceutical compositions containing the novel antioxidant or the nucleic acid constructs, and methods of relieving oxidative stress by administration of the antioxidants, the nucleic acid constructs encoding same or the pharmaceutical composition containing same to a subject in need thereof are disclosed.
Claims197
A method of evaluating a potential of a haptoglobin derived polypeptide in reducing oxidation induced by oxygenized hemoglobin, the method comprising:
- reacting hemoglobin with an oxidizable substrate in a presence and an absence, and/or in a presence of varying concentrations of the haptoglobin derived polypeptide;
- and
- determining an effect of said presence and said absence, and/or said presence of said varying concentrations of the haptoglobin derived polypeptide on oxidation of said oxidizable substrate, thereby evaluating the potential of the haptoglobin derived polypeptide in reducing the oxidation induced by the hemoglobin.
An antioxidant compound comprising a polypeptide having an amino acid sequence derived from an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the antioxidant compound being free of amino acid sequences derived from a beta subunit of a haptoglobin protein.
An antioxidant compound comprising a polypeptide having an amino acid sequence derived from a portion of an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said alpha subunit of said haptoglobin protein sequence.
An antioxidant compound comprising a polypeptide having an amino acid sequence derived from a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the antioxidant compound being free of amino acid sequences derived from an alpha subunit of a haptoglobin protein.
An antioxidant compound comprising a polypeptide having an amino acid sequence derived from a portion of a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said beta subunit of a haptoglobin protein sequence.
A method of reducing oxidative stress in a subject in need, the method comprising administering to the subject an antioxidant compound that comprises a polypeptide having an amino acid sequence derived from an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the antioxidant compound being free of amino acid sequences derived from a beta subunit of a haptoglobin protein.
A method of reducing oxidative stress in a subject in need, the method comprising administering to the subject an antioxidant compound that comprises a polypeptide having an amino acid sequence derived from a portion of an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said alpha subunit of said haptoglobin protein sequence.
A method of reducing oxidative stress in a subject in need, the method comprising administering to the subject an antioxidant compound that comprises a polypeptide having an amino acid sequence derived from a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the antioxidant compound being free of amino acid sequences derived from an alpha subunit of a haptoglobin protein.
A method of reducing oxidative stress in a subject in need, the method comprising administering to the subject an antioxidant compound that comprises a polypeptide having an amino acid sequence derived from a portion of a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said beta subunit of a haptoglobin protein sequence.
A nucleic acid construct comprising:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the polynucleotide being free of amino acid sequences derived from a beta subunit of a haptoglobin protein;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide.
A nucleic acid construct comprising:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from a portion of an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said alpha subunit of said haptoglobin protein sequence;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide.
A nucleic acid construct comprising:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the antioxidant compound being free of amino acid sequences derived from an alpha subunit of a haptoglobin protein;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide.
A nucleic acid construct comprising:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from a portion of a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said beta subunit of a haptoglobin protein sequence;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide.
A method of reducing oxidative stress in a subject in need thereof, the method comprising administering to the subject a nucleic acid construct that comprises:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the polynucleotide being free of amino acid sequences derived from a beta subunit of a haptoglobin protein;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide, so as to direct expression of said polypeptide by at least one cell type of the subject.
A method of reducing oxidative stress in a subject in need thereof, the method comprising administering to the subject a nucleic acid construct that comprises:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from a portion of an alpha subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said alpha subunit of said haptoglobin protein sequence;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide, so as to direct expression of said polypeptide by at least one cell type of the subject.
A method of reducing oxidative stress in a subject in need thereof, the method comprising administering to the subject a nucleic acid construct that comprises:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, the antioxidant compound being free of amino acid sequences derived from an alpha subunit of a haptoglobin protein;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide, so as to direct expression of said polypeptide by at least one cell type of the subject.
A method of reducing oxidative stress in a subject in need thereof, the method comprising administering to the subject a nucleic acid construct that comprises:
- a first polynucleotide encoding a polypeptide having an amino acid sequence derived from a portion of a beta subunit of a haptoglobin protein sequence, said polypeptide being capable of reducing oxidation induced by oxygenized hemoglobin, said polypeptide being free of remaining portions of said beta subunit of a haptoglobin protein sequence;
- and
- a second polynucleotide harboring a promoter operably linked to said first polynucleotide, so as to direct expression of said polypeptide by at least one cell type of the subject.
Dependencies are inferred from the claim text.