The Brigham and Women's Hospital, Inc.

Duke University

Montana State University

The Research and Development Intstitute

David J Singel

Jonathan S Stamler

Joseph Loscalzo

Daniel Simon

Johnathan Stamler

Contrary to current opinion that nitrite in general oxidizes hemoglobin with elimination of active nitric oxide, deoxygenated hemoglobin reacts with low concentration inorganic nitrite to produce very stable iron nitrosyl hemoglobin which on delivery into the body is converted to a hemoglobin capable of nitric oxide delivery and provides vasodilator and antiplatelet activity. This provides basis for ameliorated risk blood product transfusions.

Method of co-infusing a deoxygenated hemoglobin containing blood substitute and inorganic nitrite

Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use of S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

Nitrosylation of protein SH groups and amino acid residues as a therapeutic modality

Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use if S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

Nitrosated and nitrosylated heme proteins

Nitrosylation of protein SH groups and amino acid residues as a

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Bozeman, MT, United States of America

David J Singel