Cornell University

Wisconsin Alumni Research Foundation

The United States of America as Represented by the Secretary of

The United States of America as Represented by the Department of Health

The University of British Columbia

University of Alberta

Jon C Clardy

Jo E Handelsman

Haiyin He

Richard G Powell

Kenneth L Mikolajczak

Jungwon Choi

Laura Silo-Suh

Ellen K Mantus

Bruce W Zilkowski

Michael R Boyd

Raymond John Andersen

Theresa M Allen

Robert M Goodman

John H Cardellina, Ii

Richard W Fuller

E Dilip De Silva

Julie S Racok

Linda S Brinen

Kenneth M Snader

Doreen E Gillespie

Alan D Bettermann

Sean F Brady

Yael Asscher

Disclosed are triaryl cationic compounds that exhibit broad spectrum antibiotic and antifungal activity, pharmaceutical compositions containing the compounds, and methods of treating bacterial and fungal infections using the compounds. The compounds were initially isolated by screening a 25,000-member bacterial artificial chromosome (BAC) library of environmental (eDNA) from soil. At least one clone produced a dark brown melanin-like compound that was found to have antibiotic activity. The compounds were isolated and synthesized de novo. From within the positive clone, a single open reading frame that shares extensive sequence similarity with members of the 4-hydroxyphenylpyruvate family of enzymes was found to be necessary and sufficient to confer the production of at least one of the subject compounds on

Triaryl cation antibiotics from environmental DNA

The invention relates to the human protein FRAP, and in particular to the FKBP12-rapamycin binding domain thereof and to the ternary complex formed by the FRB domain, rapamycin and FKBP12. A new crystalline composition comprising the ternary complex, coordinates defining its three dimensional structure in atomic detail, and uses thereof are disclosed.

Crystalline frap complex

A biocontrol bacteria, Bacillus cereus ATCC 53522, has been found to naturally synthesize two antibiotics, here designated zwittermicin A and antibiotic B. Zwittermicin A is a 396 dalton linear aminopolyol, a class of metabolite previously unknown in B. cereus. Antibiotic B is an aminoglycoside. Both antibiotics exhibit inhibitory activity on many fungal and bacterial pathogens.

Fungicidal toxins from biocontrol bacteria

Crystalline FRAP complex

Cytotoxic metabolites are isolated by extraction and chromatography from a marine sponge of the same species as that deposited in the Zoological Museum of the University of Amsterdam under reg. no. ZMA POR. 10883. The isolated compounds belong to the genus of compounds having the structure: ##STR1## wherein R is C.sub.6 -C.sub.12 alkyl or C.sub.6 -C.sub.12 alkenyl having 1 or 2 double bonds, which may be interrupted with one or more imino groups and which may be substituted with one or more substituents selected from the group consisting of amino, carboxyl, hydroxy, imino and oxo.

Biologically active amides containing a bicyclo moiety

The present invention relates to a new antitumor compound, a method for isolating same from a red alga, antitumor compositions containing same and methods of using same for treating patients with cancer. The compound of the present invention is 6(R)-bromo-3(S)-bromomethyl-7-methyl-2,3,7-trichloro-1-octene.

Antitumor compound, compositions and method of use

Novel thioimidazoles are 5-carboxyaldehyde-1-methyl-4-(phenylmethyl)thioimidazole and 5-(.alpha.-aminoacetyl)-1-methyl-4-(phenylmethyl)thioimidazole acid addition salt. The latter is prepared from the former by steps comprising Grignard addition to form 5-(1-hydroxyethyl)-1-methyl-4-(phenylmethyl)thioimidazole, oxidizing the hydroxy compound to form the corresponding ketone, brominating under acidic conditions to form the bromoacetyl derivative, converting the bromo in the bromoacetyl derivative to N,N-diformylamino and then hydrolyzing. The latter thioimidazole is an intermediate for forming 5-methylimidazo[4,5-e]-1,2-thiazin-4(5H)-one, that is neamphine, and for forming 3-chloro-(5-methylimidazo) [4,5-e]-1,2-thiazin-4(5H)-one, that is 3-chloroneamphine.

Thioimideazoles useful as intermediates for preparing thiazine

5-Methylimidazo[4,5-e]-1,2-thiazin-4(5-H)-one, having the structure ##STR1## a cytotoxic metabolite of the marine sponge Neamphius huxleyi, has been isolated from the sponge by extraction and chromatography.

Biologically active thiazine

Members of a novel class of organic nitriles related to an indole alkaloid of Dithyrea wislizenii (Cruciferae) have been discovered to be patent feeding inhibitors of the fall armyworm and European corn borer.

Organic nitriles as insect antifeedants

Members of a novel class of organic nitriles related to an indole alkoaloid of Dithyrea wislizenii (Cruciferae) have been discovered to be potent feeding inhibitors of the fall armyworm and European corn borer.

Growing community of inventors

Ithaca, NY, United States of America

Jon C Clardy