Process for producing apelin

Details Process for producing apelin Process for producing apelin

C - Chemistry, Metallurgy

12

N

C12N 15/62 (2006.01) C07K 1/107 (2006.01) C07K 1/12 (2006.01) C07K 14/47 (2006.01) C07K 14/50 (2006.01) C07K 19/00 (2006.01) C12N 1/21 (2006.01) C12N 15/12 (2006.01) C12N 15/18 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2353560

The present invention provides a production method advantageous in producing Apelin on an industrial scale in large amounts. The present invention relates to a method for producing Apelin or a salt thereof, comprising subjecting a fused protein or peptide consisting of a protein or peptide having N-terminal cysteine with Apelin optionally having an optionally oxidized methionine residue at the N-terminus thereof joined to the N-terminus of the protein or peptide to a cleavage reaction for the peptide bond on the amino group side of the cysteine residue. Using the production method of the present invention, it is possible to produce on an industrial scale in large amounts Apelin that can be used as a therapeutic/preventive agent for such diseases as various forms of dementia, including senile dementia and cerebrovascular dementia, depression, hyperkinetic (minimal brain damage) syndrome, disturbance of consciousness, anxiety disorder, schizophrenia, phobia, impairments of growth hormone secretion, hyperphagia, polyphagia, hypercholesterolemia, hyperglyceridemia, hyperlipidemia, hyperprolactinemia, hypoglycemia, hypopituitarism, pituitary dwarfism, diabetes mellitus, cancers, pancreatitis, renal diseases, Turner's syndrome, neurosis, rheumatoid arthritis, spinal injury, transient cerebral ischemic attack, amyotrophic lateral sclerosis, acute myocardial infarction, spinocerebellar deformation, bone fractures, wounds, atopic dermatitis, osteoporosis, asthma, epilepsy, infertility, arteriosclerosis, pulmonary emphysema, pulmonary edema, and milk secretion insufficiency, and can also be used as a hypnotic sedative, a postoperative nutritional status improving agent, a hypertensive, a hypotensive, a preventive or therapeutic drug for HIV infection, AIDS, etc., and the like.

L'invention concerne un procédé permettant de fabriquer industriellement l'apeline à grande échelle. Ce procédé de fabrication de l'apeline et de ses sels est caractérisé en ce qu'une protéine ou un peptide fusionnés construit par ligature de l'apeline possédant éventuellement un résidu de méthionine au niveau de sa terminaison N, et pouvant être oxydé au niveau de la terminaison N d'une protéine ou d'un peptide présentant de la cystéine au niveau de ladite terminaison N, est soumis à une réaction de clivage de la liaison peptidique du groupe latéral amino du résidu de la cystéine. L'invention concerne également le procédé de fabrication industrielle et à grande échelle de l'apeline qui peut être utilisé comme médicament, préventif, etc. contre des maladies spécifiques.

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