Takeda Chemical Industries, Inc.

Abbott Laboratories Corporation

Takeda Limited Industries, Ltd.

Tsunehiko Fukuda

Masahiko Fujino

Susumu Shinagawa

Shizue Nakagawa

Osamu Nishimura

Hiroyuki Watanabe

Yukio Fujisawa

Shigehisa Taketomi

Kazuo Nakahama

Tsutomu Kurokawa

Shigeru Kobayashi

Ken-ichi Kuroshima

Masato Kuriyama

Nobuyuki Koyama

Chieko Kitada

Akira Fujishima

Iwao Yamazaki

Takao Yamada

Masahiro Kawase

Yuri Oshika

Obayashi, Mikihio

Junko Habashita

A cysteine-free peptide is produced by producing a fused protein comprising a protein having cysteine at its N-terminal and a cysteine-free peptide ligated to the N-terminal and subsequently subjecting the fused protein to a reaction for cleaving the peptide linkage.

Method for producing a biologically active recombinant cysteine-free peptide

Cysteine protease inhibitor

Disclosed is a parathyroid hormone (PTH) (1-34) derivative in which at least the amino acid residue at the 10-position is substituted by an acidic amino acid residue. The derivatives of the present invention showing potent cAMP-producing activity and bone formation activity, and thus are useful as therapeutic agents for bone diseases, etc.

Parathyroid hormone derivatives and their use

Method for producing a biologically active recombinant cysteine-free

Disclosed are (1) a human parathyroid hormone mutein which comprises at least one modification selected from the group consisting of (i) deletion of 3 to 6 amino acid residues on the N-terminal side in the amino acid sequence of human parathyroid hormones, (ii) substitution of another lipophilic amino acid residue for at least one methionine residue in the amino acid sequence, and (iii) substitution of a cysteine residue for one amino acid residue within the region of amino acid residue Nos. 34 to 47 in the amino acid sequence; (2) a recombinant DNA having a nucleotide sequence coding for the human parathyroid hormone mutein described in (1); (3) a vector containing the recombinant DNA described in (2); (4) a vector in which the recombinant DNA described in (2) is inserted into a region controlled by an E. coli T7 promoter; (5) a transformant which is transformed by the recombinant DNA described in (2); and a process for producing a human parathyroid hormone mutein which comprises cultivating the transformant described in (5) in a culture medium.

Human parathyroid hormone muteins and production thereof

A mutein resulting from substitution of cysteins for at least one of the constitutional amino acids has a high stability, and can serve well as a pharmaceutical, such as a healing promoting agent for wounds.

bFGF mutein and its production

Disclosed are (1) a DNA containing a synthetic gene for expression of human parathyroid hormone represented by the following DNA sequence:

Synthetic gene coding for human parathyroid hormone

Disclosed are (A) an antibody to a peptide consisting of 8 to 9, or 12 to 14 successive amino acids from a polypeptide having nerve growth factor-like activity, (B) a method for producing the antibody, (C) a cloned hybridoma which produces the antibody, (D) a method for producing the cloned hybridoma, (E) a conjugate of the above mentioned peptide with a carrier protein, and (F) a method for purifying, and a method for detecting and assaying a polypeptide having nerve growth factor-like activity.

Antibodies to peptides having NGF-like activity, and use thereof

Disclosed are (A) an antibody to a peptide including at least 8 successive amino acids of an amino acid sequence represented by formula

Antibodies to peptides having NGF-like activity, said antibodies having

Parathyroid hormone (PTH) derivatives represented by the general formula: ##STR1## or a salt thereof, wherein R.sub.1 represents Ser or a D-.alpha.-amino acid residue of 4 or less carbon atoms; R.sub.2 represents a tetrapeptide chain which contains at least one water-soluble .alpha.-amino acid residue; R.sub.3 represents a tripeptide chain which contains at least one water-soluble .alpha.-amino acid residue; and R.sub.4 represents an aromatic amino acid residue or an amide thereof, except that R.sub.1 is Ser when R.sub.2 is His-Leu-Asn-Ser, R.sub.3 is E-F-G wherein E is Arg or His, F is Lys or His, G is Lys, Leu or Gln, are disclosed. The parathyroid hormone derivatives of the present invention are stable and have high biological activity, therefore they are useful as drugs for bone diseases and the like.

Parathyroid hormone derivatives

Disclosed are peptides and salts thereof represented by general formul ##STR1## wherein R.sub.1 represents Ser or Aib; R.sub.2 represents Met or a naturally occurring hydrophobic amino acid; R.sub.3 represents Leu, Ser, Lys or an aromatic amino acid; R.sub.4 represents Gly or a D-.alpha.-amino acid; R.sub.5 represents Lys or Leu; R.sub.6 represents Met or a naturally occurring hydrophobic amino acid; R.sub.7 represents Glu or a basic amino acid; R.sub.8 represents Val or basic amino acid; R.sub.9 represents Trp or 2-(1,3-dithiolane-2-yl)Trp; R.sub.10 represents Arg or His; R.sub.11 represents Lys or His; R.sub.12 represents Lys, Gln or Leu; and R.sub.13 represents Phe or Phe-NH.sub.2 ; except that simultaneously R.sub.1 consists of Ser, R.sub.2 consists of Met, R.sub.3 consists of Leu, R.sub.4 consists of Gly, D-Ala or D-Pro, R.sub.5 consists of Lys, R.sub.6 consists of Met, R.sub.7 consists of Glu, R.sub.8 consists of Val, R.sub.9 consists of Trp, R.sub.10 consists of Arg, R.sub.11 consists of Lys and R.sub.12 consists of Lys. The parathyroid hormone (1-34) analogs are useful in hormone therapy.

An indole group in an amino acid or a peptide can be protected with a group shown by the formula: ##STR1## wherein R.sub.1 and R.sub.5 each is hydrogen, methyl or methoxy; R.sub.2 and R.sub.4 each is hydrogen or methyl; and R.sub.3 is methyl or methoxy, and said group may easily be removed without affecting the amino acid or the peptide to be derived from the protected amino acid or peptide. Thus, the present invention is useful in the synthesis of a peptide containing an indole group.

Indole derivatives and a method for production of peptides

In an amino acid having .omega.-amino group protected with a protective group or a peptide having the residue of such a protected amino acid, the improvement according to which the protective group is p-methylbenzylsulfonyl group. The .omega.-amino acids protected with p-methylbenzylsulfonyl or the peptides having residues of such protected amino acids are useful for production of various peptides by liquid phase method as well as by solid-phase method, because the protective group has specific selectivity of remaining stable under the conditions commonly employed in the removal of .alpha.-aminoprotecting group but is cleaved smoothly in a good yield by hydrogen fluoride without exerting untoward unfluences upon peptides.

Protected amino acids or peptides

The novel nonapeptide amide derivatives of the formula

Growing community of inventors

Kyoto, Japan

Tsunehiko Fukuda