The Medical College of Wisconsin, Inc.

Mcw Research Foundation, Inc.

Yang Shi

John E Baker

Hao Xu

Hao Zhang

Kirkwood A Pritchard, Jr

The present invention provides peptide-based peroxidase inhibitors having the formula AA-AA-AA, wherein AAis a positively charged, negatively charged or neutral amino acid, AAis a redox active amino acid, and AAis an amino acid possessing a reducing potential such that AAis capable of undergoing a redox reaction with a radical of amino acid AAor 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.

Peptide-based peroxidase inhibitors and methods of using same

The present invention provides peptide-based peroxidase inhibitors having the formula AA-AA-AA, wherein AA1 is a positively charged, negatively charged or neutral amino acid, AAis a redox active amino acid, and AAis an amino acid possessing a reducing potential such that AAis capable of undergoing a redox reaction with a radical of amino acid AAor 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.

Peptide based peroxidase inhibitors and methods of using same

A therapeutic or prophylactic treatment method of ischemia, such as due to myocardial infarction, by administering thrombopoietin, alone or in combination with other drugs, to a patient suffering from or at risk of cardiac injury, such as myocardial ischemia. The thrombopoietin is administered in a concentration such that the subject's platelet count or production of platelets is not significantly affected.

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Wauwatosa, WI, United States of America

Yang Shi