Asahi Kasei Kogyo Kabushiki Kaisha

Torao Ishida

Minoru Akiyama

Yoshio Sakurai

Shigeru Tsukagoshi

Chisei Shibuya

Mitsuru Shibukawa

Hiroshi Hayashi

Kunihiko Ishii

Daikichi Nishimura

Takashi Shirai

Kageyasu Akashi

Koichi Yoshida

Hirataka Itoh

Toshiaki Sugawara

Yukiji Shimojima

Tadaaki Ooka

Takumi Sano

An active protein can be easily, safely produced by a method comprising providing a first peptide fragment having a first amino acid sequence corresponding to part of an active protein and a second peptide fragment having a second amino acid sequence corresponding to the remaining part of the active protein, at least one of said first peptide fragment and said second peptide fragment being one which has been obtained by recombinant DNA technique or has been obtained by a method comprising producing a predetermined peptide fragment by recombinant DNA technique and deleting from or adding to said predetermined peptide fragment at its N-terminus at least one amino acid residue; and linking said first peptide fragment at its C-terminus to said second peptide fragment at its N-terminus. The method of the present invention may be practiced, with further advantages, by predeterming said first peptide fragment and said second peptide fragment so that a first occurring methionine residue subsequent to the N-terminal amino acid residue of the active protein constitutes the N-terminal amino acid of the amino acid sequence of said second peptide fragment, or so that an amino acid residue positioned near the first occurring methionine residue subsequent to the N-terminal amino acid residue of the desired protein on the side of the N-terminus of the desired protein constitutes the N-terminal amino acid residue of said second peptide fragment.

Method for producing an active protein

A novel physiologically active peptide represented by the following formula:

Physiologically active peptide

AI-77 compounds, pharmaceutically acceptable salts thereof, and a process for the preparation thereof are described, said compounds having the formulae ##STR1## wherein: X is NR.sub.6 or O; Y is NHR.sub.5 or combine with Z to provide a link for bonding C and C; Z is H or combines with Y to provide a link for bonding C and C; R.sub.1, R.sub.3 and R.sub.5 are each H, R', --CH.sub.2 R, or --COR; R.sub.6 is H or R; R.sub.7 is H, R or CH.sub.2 R; R is a hydrocarbon group consisting of a saturated or unsaturated straight or branched aliphatic group of C.sub.1 to C.sub.17, an aromatic group of C.sub.6 to C.sub.10, a cage type group of C.sub.7 to C.sub.10, a monocyclic aliphatic group of C.sub.3 to C.sub.8, an aromatic-aliphatic group of C.sub.7 to C.sub.15, a heterocyclic hydrocarbon of C.sub.1 to C.sub.9, wherein the above hydrocarbons can be substituted with one or more groups selected from halogen, oxo, carboxyl, hydroxyl, a saturated or unsaturated straight or branched aliphatic group of C.sub.1 to C.sub.5, an aromatic group of C.sub.6 to C.sub.10, a monocyclic aliphatic group of C.sub.3 to C.sub.8, an aromatic-aliphatic group of C.sub.7 to C.sub.11, alkoxy of C.sub.1 to C.sub.5, thioalkoxyl of C.sub.1 to C.sub.5, carboalkoxyl of C.sub.1 to C.sub.6, acyl of C.sub.1 to C.sub.5, acyloxy of C.sub.2 to C.sub.6 and a heterocyclic group of C.sub.1 to C.sub.9 ; R' is the same as R exclusive of those groups wherein unsaturated carbon or tertiary carbon is directly bonded to O or N; R.sub.2 is H, or combines with T.sub.1 to provide a link for bonding C and O in a lactone ring; T.sub.1 is OH or combines with R.sub.2 to provide a link for bonding C and O in a lactone ring; R.sub.4 is H or combines with T.sub.2 to provide a link for bonding C and O in a lactone ring; and T.sub.2 is OH or combines with R.sub.4 to provide a link for bonding C and O in a lactone ring; and pharmaceutically acceptable salts thereof.

AI-77 Compounds and pharmaceutically acceptable salts thereof

An 1,3,4-thiadiazole-5-thiol ester of the formula, ##STR1## wherein R is a hydrogen atom or a methyl group, a process for their preparation and a process for preparing a cephalosporin compound of the formula, ##STR2## wherein R is the same as defined above, using the above described 1,3,4-thiadiazole-5-thiol ester.

Novel thiol esters and process for preparing cephalosporin compounds

Novel 7.alpha.-methoxycephalosporin derivatives having a high antimicrobial activity. They are useful for the medical treatment of diseases infected by gram-positive bacteria and gram-negative bacteria. More particularly, they show an antimicrobial activity against bacteria such as Eschericha coli Proteus, Citrobacter and Enterobacter which bacteria have resistance to the conventionally employed cephalosporins, and they are effective for the medical treatment of diseases infected by these bacteria. Such 7.alpha.-methoxycephalosporin derivatives are prepared by a relatively simple method.

7.alpha.-Methoxycephalosporin derivatives

Compounds represented by formula (I) ##STR1## wherein one of Z.sub.1 ', Z.sub.2 ', Z.sub.3 ' and Z.sub.4 ' represents R, another one of Z.sub.1 ', Z.sub.2 ', Z.sub.3 ' and Z.sub.4 ' represents Z, and the remaining two moieties of Z.sub.1 ', Z.sub.2 ', Z.sub.3 ' and Z.sub.4 ' represents a hydrogen atom and/or a protective group, one of R and Z represents A.sub.1 and the other represents A.sub.2, A.sub.1 being an acyl group having 14 to 22 carbon atoms which does not contain a carboxylic group and A.sub.2 being an acyl group having 2 to 14 carbon atoms and having one carboxyl group, X represents a hydrogen atom or a halogen atom (hereinafter referred to as Compound Ia); a 2,2'-anhydro product of Compound Ia wherein Z.sub.2 ' represents a hydrogen atom (hereinafter referred to as Compound Ib); an arabinosylation product of Compound Ia (hereinafter referred to as Compound Ic); a deamination product of Compound Ia (hereinafter referred to as Compound Id); a 2'-deoxy product of Compound Id wherein Z.sub.2 ' represents a hydrogen atom (hereinafter referred to as Compound Ie); a salt of Compound Ia, Ib, Ic, or Id or Ie having an A.sub.2 group with a base (hereinafter referred to as Compound If); and a salt of Compound Ia, Ib or Ic wherein Z.sub.1 ' represents a hydrogen atom with an acid (hereinafter referred to as Compound Ih); and processes for preparing the same.

Diacylnucleosides and process for preparing the same

A compound represented by the formulae: ##STR1## wherein R.sub.1 and R.sub.2 are as defined hereinafter, useful as an anti-cancer or anti-tumor agent.

5-Fluorouracil derivatives

A nucleotide derivative represented by the general formula: ##STR1## wherein R represents an acyl group having 14 - 22 carbon atoms and having an aliphatic acyl moiety; X represents a hydrogen atom, a halogen atom, an alkyl group having 1 - 4 carbon atoms, or a trifluoromethyl group; and at least one, but not all, of Y.sub.1, Y.sub.2, and Y.sub.3 represents a phosphate, a pyrophosphate, a triphosphate, or a salt thereof, the balance of Y.sub.1, Y.sub.2 and Y.sub.3 representing a hydroxyl group; or in case of ribosyl, Y.sub.1 and Y.sub.3, or Y.sub.2 and Y.sub.3 represent, at the same time, the aforesaid phosphate, pyrophosphate, triphosphate or salt thereof and the remaining group of Y.sub.1, Y.sub.2 or Y.sub.3 represents a hydroxyl group; or in case of arabinosyl, Y.sub.1 and Y.sub.2, or Y.sub.2 and Y.sub.3 represent, at the same time, the aforesaid phosphate, pyrophosphate, triphosphate or salt therof and the remaining group of Y.sub.1, Y.sub.2 or Y.sub.3 represents a hydroxyl group. The nontoxic salts of these phosphates are useful as an antileukemialagent for mice which is soluble in water and has high stability.

Cytidine nucleotide derivatives

N.sup.4 -Acyl-1-.beta.-D-arabinofuranosylcytosine-5'-esters represented by the formula ##STR1## wherein R.sup.1 represents an acyl group having 3 to 28 carbon atoms and R.sup.2 represents an XCH.sub.2, XCH.sub.2 CH.sub.2 or CH.sub.3 CHX group, wherein X represents a halogen atom, a (CH.sub.3).sub.2 N or (C.sub.2 H.sub.5).sub.2 N group.

N.sup.4 Acyl-1-arabinofuranosylcytosine-5'-esters

An N.sup.4 -acyl-1-.beta.-D-arabinofuranosylcytosine having the following formula ##SPC1## Wherein R is an aliphatic acyl group having 3 to 35 carbon atoms. The compounds of this invention are useful as a cancer chemotherapeutic agent for controlling tumors, e.g., in mice, an insecticide, and a fungicidal surface active agent.

Growing community of inventors

Fuji, Japan

Torao Ishida