The Upjohn Co.

Pharmacia & Upjohn Company

Alice L Laborde

Lester A Dolak

Thomas M Castle

Oldrich K Sebek

Franklin B Shilliday

Scott E Truesdell

Alexander D Argoudelis, Deceased

Fritz Reusser

Betty R Hannon

Charles K Marschke

Thomas F Brodasky

Heinrich Josef Schostarez

Scott D Larsen

Jerry R Colca

Rolf F Kletzien

Alexander D Argoudelis

Matthew L Peach

Peter K Harris

Howard R Miller

The present invention provides for a polypeptide aggregation screening assay for the purpose of detecting modulators of polypeptide aggregation, which can provide for new therapies in pathologic states associated with polypeptide aggregation, especially considered is Alzheimer's Disease.

Time-resolved fluorescence assay for the detection of multimeric forms of A-beta 1-40

Antibiotic 10381a,, wherein R is hydrogen, is a cytosine-containing antibiotic producible by culturing the novel microorganism,in an aqueous medium and isolation thereof. Derivatives wherein R is a C,to C,alkyl ester of antibiotic 10381a,, are also disclosed along with the pharmaceutically acceptable salts of both the native and esterified forms. Antibiotic 10381a,inhibits the growth of selected species of yeast, fungi and bacteria. This invention also relates to a novel process for the preparation of the antibiotics 10381b and to a method of using antibiotics 10381b to promote growth in meat-producing animals. These antibiotics are also obtained by the fermentation of a nutrient medium with the novel microorganism,and are active against selected species of bacteria.

Antibiotic 10381A, and process for the preparation of anitbiotics 10381B

Antibiotic 10381a.sub.1, wherein R is hydrogen, is a cytosine-containing antibiotic producible by culturing the novel microorganism Streptomyces arginensis in an aqueous medium and isolation thereof. Derivatives wherein R is a C.sub.1 to C.sub.3 alkyl ester of antibiotic 10381a.sub.1, are also disclosed along with the pharmaceutically acceptable salts of both the native and esterified forms. Antibiotic 10381a.sub.1 inhibits the growth of selected species of yeast, fungi and bacteria. This invention also relates to a novel process for the preparation of the antibiotics 10381b and to a method of using antibiotics 10381b to promote growth in meat-producing animals. These antibiotics are also obtained by the fermentation of a nutrient medium with the novel microorganism Streptomyces arginensis and are active against selected species of bacteria.

Antibiotic 10381A.sub.1 and process for the preparation of antibiotics

Use of antibiotics 10381b to promote growth

The present invention provides some novel 4-hydroxycoumarin-3-carboxamide derivatives and the use of a broad class of 4-hydroxycoumarin-3-carboxamide derivatives for the treatment of a patient suffering from or susceptible to diabetes mellitus.

4-hydroxycoumarin-3-carboxamides for the treatment of diabetes mellitus

Process for the preparation of antibiotics 10381B

Novel antibiotic U-68,204 is produced in a fermentation under controlled conditions using a biologically pure culture of the microorganism Streptomyces thiolactonus, NRRL 15439. This antibiotic is active against various Gram-positive bacteria. Thus, antibiotic U-68,204 can be used in various environments to eradicate or control such bacteria.

Antibiotic producing Streptomyces thiolactonus

Composition of matter and process

Novel antibiotic U-64,864 producible in a fermentation under controlled conditions using a biologically pure culture of the microorganism Streptomyces braegensis Dietz sp.n., NRRL 12567. This antibiotic is active against various Gram-positive bacteria, for example, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. Thus, antibiotic U-64,864 can be used in various environments to eradicate or control such bacteria.

Antibiotic producing streptomyces

Novel antibiotic U-64,767 producible in a fermentation under controlled conditions using a biologically pure culture of the microorganism Streptomyces macronensis Dietz sp.n., NRRL 12566. This antibiotic is active against various Gram-positive bacteria, for example, Staphylococcus aureus and Streptococcus pyogenes. It is also active against the Gram-negative bacterium Streptococcus pneumoniae. Thus, antibiotic U-64,767 can be used in various environments to eradicate or control such bacteria.

Process for production of antibiotic U-64,767 using Streptomyces

Novel antibiotic 3-trehalosamine (U-59,834) producible in a fermentation under controlled conditions using the new microorganism Nocardiopsis trehalosei sp. nov., NRRL 12026. This antibiotic is active against Gram-positive bacteria, for example, Staphylococcus aureus, Bacillus subtilis, and Diplococcus pneumoniae. Thus, 3-trehalosamine can be used in various environments to eradicate or control such bacteria. Antibiotic 3-trehalosamine can be shown by the following structural formula: ##STR1##

Process of producing 3-trehalosamine by fermentation

Biologically pure culture of Nocardiopsis trehalosei sp. nov.

3-Trehalosamine compounds

Growing community of inventors

Kalamazoo, MI, United States of America

Alice L Laborde