Ciba-geigy Corporation

Novartis Corporation

Ucp Gen-pharma Ag

Hans Rink

Peter Sieber

Bruno Kamber

Markus G Grutter

Manfred Liersch

Bernd Meyhack

Walter Marki

Hans Fritz

Albert Schmitz

Werner Rittel

Sefik Alkan

Klaus Muller

Francois Meyer

Derek E Brundish

Walter M&auml;rki

Paul H Steenbergh

Cornelis J Lips

Hendrik S Jansz

Ursula Seem&uuml;ller

John Peter Priestle

The invention relates to DNA sequences which code an eglin, expression plasmids containing such DNA sequences, hosts transformed with such expression plasmids, novel eglin compounds produced from such transformed hosts, monoclonal antibodies against eglins, hybridoma cells which produce such antibodies, and test kits for immunoassays containing such antibodies, and furthermore the processes for their preparation and a process for the preparation of eglins with the aid of the transformed hosts. The eglins which can be prepared according to the invention have useful pharmacological properties.

Process for preparing recombinant eglin, protease inhibitor

The invention relates to DNA sequences that code for the amino acid sequence of the thrombin inhibitor hirudin, hybrid vectors containing such DNA sequences, host cells transformed with such hybrid vectors, novel polypeptides with thrombin-inhibiting activity produced from such transformed host cells, processes for the manufacture of these DNA sequences, hybrid vectors and transformed host cells, and processes for the manufacture of these thrombin-inhibitors using the transformed host cells. The hirudin compounds that can be produced according to the invention have valuable pharmacological properties.

Process for the manufacture of thrombin inhibitors

Peptide derivatives corresponding to the carboxy terminal sequence of

Peptides of formula I ##STR1## in which R is hydrogen or acetyl and X is an amino acid sequence of formula -Ser-Leu-Asp-Ser-Pro-Arg-Ser- (Ia) or of formula -Arg-Ile-Ile-Ala-Gln- (Ib), and salts of such compounds, can be used for the treatment of diseases involving bone degeneration.

Flanking peptides of calcitonin and processes for their manufacture

A synthetic resin based on a polystyrene that can be used as a support for solid phase peptide synthesis and that has been cross-linked with from 0 to 5 mol % of divinyl benzene, characterized in that it has been substituted at benzene rings of its skeletal structure by groups of the formula ##STR1## in which X represents --O-- or --NH-- and R represents C.sub.1 -C.sub.4 -alkyl, as a support renders possible the solid phase synthesis of peptides and peptide amides that are, if desired, protected at the N-terminal and/or at other functional groups. The resin is manufactured by reaction of a customary chloromethylated polystyrene resin with an alkali metal salt of the corresponding 4-hydroxybenzophenone and subsequent reduction of the carbonyl group and, optionally, amination.

2,4-dimethoxy-4'-hydroxy-benzophenone

Synthetic polystyrene resin and its use in solid phase peptide synthesis

Described are peptides that have, as partial sequence of a larger peptide, or exclusively, the amino acid sequence of the formula I ##STR1## in which the cysteine residues can form intra- or inter-molecular disulphide bridges, and derivatives thereof having an amidated terminal carboxy group and/or an acylated terminal amino group, and their salts, DNA sequences that code for the mentioned peptides, micro-organisms that contain these DNA sequences, processes for the manufacture thereof, pharmaceutical preparations that contain the mentioned peptides in the form of their amides, and the use of these peptide-amides for the treatment of coronary circulation disorders and bone metabolism disorders.

Oligopeptides and intermediates and processes for their manufacture

Acylpeptides derived from somatostatin or from a derivative thereof having analogous action, in which the amino acids sequence is modified by omitting individual amino acids and/or by exchanging them for other amino acids, and in which the .epsilon.-amino group of the lysine residue in the 9-position, and optionally also the .epsilon.-amino group of the lysine residue in the 4-position and/or the N-terminal .alpha.-amino group carries the acyl radical of an optionally substituted alkanecarboxylic acid, and salts and complexes thereof can be used as antidiabetics and/or for combating gastrointestinal bleeding. They are manufactured by conventional methods of peptide chemistry.

Acylpeptides

Cyclic peptides of the formula ##STR1## in which trp represents L-Trp, D-Trp, or an analogous radical which carries a halogen atom in the indole nucleus, Ac.sub.A represents hydrogen, or an acyl radical Ac of a carboxylic acid present at the .epsilon.-amino group, A represents L-Phe, D-Phe, L-Phg or D-Phg, or a corresponding radical having a substituted or saturated phenyl ring, and B represents the residue of a .gamma.- or .delta.-amino-lower alkanecarboxylic acid which may carry an optionally substituted cyclic hydrocarbyl radical Ar, and also pharmacologically tolerable salts and therapeutically acceptable complexes thereof can be used as an antidiabetic in an analogous manner to somatostatin. They can be obtained by conventional processes of peptide chemistry, especially by cyclisation of corresponding linear peptides.

Cyclooctapeptides

The somatostatin-analogous cyclic octapeptides according to the invention of the general formula ##STR1## in which trp represents L-Trp or D-Trp, in which the benzene ring may be substituted by a halogen atom, and

Cyclopeptides and pharmaceutical preparations thereof and also processes

The somatostatin-analogous peptides according to the invention of the general formula ##STR1## in which Bmp represents the desaminocysteine radical

Peptides and processes for the manufacture thereof

Sulphur-free cyclopeptides with somatostatin-analogous aminoacid partial sequences, of the formula ##STR1## in which R is Asn, Ala or de-R, trp is D-Trp or L-Trp, which can be substituted in the benzene ring by halogen atoms or nitro groups, W is a free or etherified hydroxyl group or halogen atom present as a substituent on the benzene ring of the L-phenylalanine radical, or is hydrogen, X is the radical of an .omega.-amino-lower alkane-(mono or di)-carboxylic acid or de-X and Y is the radical of an .omega.-amino-lower alkane-(mono or di)-carboxylic acid or de-Y, and also acid addition salts and complexes thereof have biological properties similar to those of somatostatin and can be used, especially in the form of pharmaceutical preparations, for the treatment of excessive secretion of somatotropin, insulin and/or glucagon. The compounds according to the invention are obtained by cyclising a corresponding linear peptide compound in which the .epsilon.-amino group of the lysine radical and, if desired, also the hydroxyl group of the threonine radical are protected and detaching the protective groups which are present.

Growing community of inventors

Riehen, Switzerland

Hans Rink