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AssigneeThe Medical College of Wisconsin, Inc.
InventorsHao Zhang, Yang Shi, Hao Xu, Kirkwood A. Pritchard, JR.
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The present invention provides peptide-based peroxidase inhibitors having the formula AA1-AA2-AA3, wherein AA1 is a positively charged, negatively charged or neutral amino acid, AA2 is a redox active amino acid, and AA3 is an amino acid possessing a reducing potential such that AA3 is capable of undergoing a redox reaction with a radical of amino acid AA2 or a retro or retro-inverso analog thereof. The result of such a combination is a highly effective inhibitor of peroxidase activity that has potent anti-inflammatory properties in widely diverse models of vascular disease and injury. Exemplary tripeptides effectively inhibit peroxidase mediated LDL oxidation, increase vasodilation in SCD mice, inhibit eosinophil infiltration and collagen deposition in asthma mice, inhibit acute lung injury, and decrease ischemic injury of the heart.
A method of inhibiting peroxidase activity in a subject, the method comprising administering to the subject a peptide-based peroxidase inhibitor having the formula AA1-AA2-AA3, wherein AA1 is a positively charged, negatively charged or neutral amino acid, AA2 is a redox active amino acid, and AA3 is an amino acid possessing a reducing potential such that AA3 is capable of undergoing a redox reaction with a radical of amino acid AA2;
A peptide-based peroxidase inhibitor having the formula AA1-AA2-AA3, wherein AA1 is a positively charged, negatively charged or neutral amino acid, AA2 is a redox active amino acid, and AA3 is an amino acid possessing a reducing potential such that AA3 is capable of undergoing a redox reaction with a radical of amino acid AA2;
A method of inhibiting peroxidase activity in a subject, the method comprising administering to the subject a peptide-based peroxidase inhibitor consisting of (a) the tripeptide KYC, or (b) the tripeptide KYC having a protecting group coupled to its amino terminus, its carboxyl terminus, or to both its amino and carboxyl termini.
Dependencies are inferred from the claim text.