Takeda Chemical Industries, Inc.

Director-general of Agency of Industrial Science and Technology

Takeda Chemical Ind., Ltd.

501 Takeda Chemical Industries, Ltd.

Tomoh Masaki

Masashi Yanagisawa

Akihiro Inoue

Yoshio Yazaki

Hiroki Kurihara

Youji Mitsui

Katsutoshi Goto

Sadao Kimura

A cloned DNA molecule is disclosed. The DNA molecule encodes a human endothelin-3 protein having the amino acid sequence: Glu-Gly-Ala-Pro-Glu-His-His-Arg-Ser-Arg-Arg-Cys-Thr-Cys-Phe-Thr-Tyr-Lys-As p-Lys-Glu-Cys-Val-Tyr-Tyr-Cys-His-Leu-Asp-Ile-Ile-Trp-Ile-Asn-Thr-Pro-Glu or any portion of said amino acid sequence containing Cys-Thr-Cys-Phe-Thr-Tyr-Lys-Asp-Lys-Glu-Cys-Val-Tyr-Tyr-Cys-His-Leu-Asp-Il e-Ile-Trp. Also disclosed is a method of producing mature endothelin-3 protein. In the method, the host cell is cultured, allowing mature endothelin-3 to accumulate in the culture medium, and the mature endothelin-3 protein is separated from the culture medium.

DNA encoding human endothelin-3, and use thereof

Disclosed are (1) a DNA sequence containing a DNA segment coding for endothelin-2 or human endothelin-3, (2) a precursor protein and a mature peptide of endothelin-2 or human endothelin-3, (3) a transformant carrying a DNA sequence containing a DNA segment coding for endothelin-2 or human endothelin-3 and (4) a method for preparing mature endothelin-2 or endothelin-3 which comprises culturing the transformant described in (3), producing and accumulating a protein in a culture medium, and collecting the same. Cells transfected or transformed with the DNA allow large amounts of endothelin-2 or endothelin-3 to be produced, which causes the advantageous production of endothelin-2 or endothelin-3. Endothelin-2 and endothelin-3 can be utilized as hypotension therapeutic agents or local vasoconstrictors to animals including humans.

Human endothelin-3 precursor protein

Disclosed are (1) a DNA sequence containing a segment coding for endothelin-2 or human endothelin-3, (2) a precursor protein and a mature peptide of endothelin-2 or human endothelin-3, (3) a transformant carrying a DNA sequence containing a DNA segment coding for endothelin-2 or human endothelin-3 and (4) a method for preparing mature endothelin-2 or endothelin-3 which comprises culturing the transformant described in (3), producing and accumulating a protein in a culture medium, and collecting the same. Cells transfected or transformed with the DNA allow large amounts of endothelin-2 or endothelin-3 to be produced, which causes the advantageous production of endothelin-2 or endothelin-3. Endothelin-2 and endothelin-3 can be utilized as hypotension therapeutic agents or local vasoconstrictors to animals including humans.

Endothelin DNA and use thereof

Endothelin-2 and a big type of endothelin-2 proteins are described. The proteins contain the amino acid sequence: Cys Ser Cys Ser Ser Trp Leu Asp Lys Glu Cys Val Tyr Phe Cys His Leu Asp Ile Ile Trp.

Endothelin

Disclosed is a vasoconstrictor peptide called Endothelin having a molecular weight of 2,500.+-.300. Endothelin contains 21 amino acid residues, wherein four cysteines form two sets of S--S bond. In order to obtain the vasoconstrictor factors of the present invention, it is preferable to culture the endothelial cells collected from the vascular inner walls in a serum-free medium. The vasoconstrictor peptides of the present invention can be utilized as hypotension therapeutic agents or local vasoconstrictors to animals including humans.

Growing community of inventors

Ibaraki, Japan

Tomoh Masaki