Daiichi Pharmaceutical Co., Ltd.

Murphy T J

R Wayne Alexander

Ken'ichi Nishida

David G Harrison

The cloning, nucleotide and deduced amino acid sequences of the gene encoding endothelial nitric oxide synthase are described. The sequence contains binding domains for calcium/calmodulin, FMN, FAD and NADPH. The enzyme has a molecular weight of 133,413 M.sub.r. The amino terminal portion of the enzyme exhibits a proline-rich region and several sites for proline-directed phosphorylation as well as a potential substrate site for acyl transferase. DNA probes prepared from the nucleic acid sequence are useful in research and diagnostically to determine the level of nitric oxide synthase mRNA expressed by endothelial cells both in cell culture and in intact tissues. These probes are also useful for detecting genetic abnormalities. The nitric oxide synthase gene is transfected into blood vessels in vivo for enhanced synthesis of nitric oxide synthase, resulting in increased production of nitric oxide. The gene is also transfected into host cells that do not normally express the enzyme for production of endothelial nitric oxide synthase in large volumes.

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Atlanta, GA, United States of America

Murphy T J