Johns Hopkins University

Mars, Incorporated

Rutgers, the State University of New Jersey

Chektec Corporation

Craig Arthur Townsend

Gary R Pasternack

Francis P Kuhajda

Amit Basak

Nicole M Parrish

Leo J Romanczyk

Evan P Lloyd

James D Dick

Micah Jeffrey Bodner

Ryan Martin Phelan

Michael Francis Freeman

Gyanu Lamichhane

Joel S Freundlich

Sean Ekins

Leo J Romancyzk, Jr

Garfield P Royer

Amit Kaushik

Pankaj Kumar

Neelakandha S Mani

Shaogang Li

Rong-feng Li

Antibacterial agents against D,D- and L,D-transpeptidases are disclosed. Pharmaceutical compositions and methods of using the same also are disclosed.

Antibacterial agents against D,D- and L,D-transpeptidases

New antimicrobials targeting L,D-transpeptidases, non-classical cysteine peptidases, have been developed and their unique chemical structures identified. Carbapenems and penems of the present invention are unique among &#x3b2;-lactams as they acylate and inhibit L,D-transpeptidases, which likely results in their superior antimicrobial potency. These new antimicrobial agents can be used alone, or in combination with other classic antimicrobial agents that target D,D transpeptidases, when treating bacterial infections.

Inhibitors of bacterial growth

The presently disclosed subject matter demonstrates that ThnG and ThnQ enzymes encoded by the thienamycin gene cluster inoxidize the C-2 and C-6 moieties of carbapenems, respectively. ThnQ stereospecifically hydroxylates PS-5 giving N-acetyl thienamycin. ThnG catalyzes sequential desaturation and sulfoxidation of PS-5, giving PS-7 and its sulfoxide. The ThnG and ThnQ enzymes are relatively substrate selective, but give rise to the oxidative diversity of carbapenems produced by, and orthologues likely function similarly in allied

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Genetically engineeredstrains with improved capabilities to produce clavulanic acid are provided. The strains are genetically engineered by disrupting newly identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes. This results in an increased intracelluar pool of the clavulanic acid precursor D-glyceraldehyde-3-phosphate (D-G3P), and increased clavulanic acid production. Clavulanic acid production may be further increased by supplying arginine to the medium in which theis grown.

This invention provides compounds and methods for treating, with said compound, a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R&#x2014;SO-Z-CO&#x2014;Y, where R is an alkyl groups having 6-20 carbon atoms, unsaturated hydrocarbon groups having 6-20 carbon atoms, or alkyl groups having 6-20 carbon atoms interrupted by at least one aromatic ring; Z is &#x2014;CH&#x2014;, &#x2014;CHCH&#x2014;, &#x2014;NH&#x2014;NH&#x2014;, &#x2014;O&#x2014;, &#x2014;&#x2014;NH&#x2014;, &#x2014;O&#x2014;NH&#x2014;, &#x2014;CH&#x2014;NH&#x2014;, &#x2014;CH&#x2014;O&#x2014;, &#x2014;NH&#x2014;O&#x2014;, &#x2014;NH&#x2014;CH&#x2014;, &#x2014;O&#x2014;CH&#x2014;, and &#x2014;CH&#x2550;CH&#x2014;; Y is &#x2014;NH, &#x2014;O&#x2014;CH&#x2014;CH, &#x2014;CO&#x2014;CO&#x2014;O&#x2014;CH, and &#x2014;O&#x2014;CH; and n is 1 or 2. It has been discovered that these compounds treat microbially-based infections caused by corynebacteria, nocardiae, rhodococcus, and mycobacteria. These compounds may be used to treat mycobacterial cells, such as, drug resistant, and pathogenicsp.

Antimicrobial compounds

Processes are disclosed for the production of linear and branched procyanidin oligomers having 'n' procyanidin monomeric units where n is 2 to 18. The processes include coupling protected, activated monomers with an unprotected monomer to produce a partially protected (4&#x2192;8) dimer. The dimer is optionally blocked, coupled with an activated protected monomer to produce a partially protected, optionally blocked trimer, and deprotected. The steps can be repeated to produce higher oligomers. Processes are also provided for producing (8&#x2192;8), (8&#x2192;6), and (6&#x2192;6) dimers and doubly branched oligomers. Crystalline 8-bromo tetra-O-benzyl (&#x2212;)-epicatechin is produced under certain conditions.

Synthetic methods for preparing procyanidin oligomers

Processes are disclosed for the production of linear and branched procyanidin oligomers having 'n' procyanidin monomeric units where n is 2 to 18. The processes include coupling protected, activated monomers with an unprotected monomer to produce a partially protected (4&#x2192;8) dimer. The dimer is optionally blocked, coupled with an activated protected monomer to produce a partially protected, optionally blocked trimer, and deprotected. The steps can be repeated to produce higher oligomers. Processes are also provided for producing (8&#x2192;8), (8&#x2192;6), and (6&#x2192;6) dimers and doubly branched oligomers. Crystalline 8-bromo-tetra-O-benzyl-(&#x2212;)-epicatechin is produced under certain conditions.

This invention provides methods for treating a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R&mdash;SO &mdash;Z&mdash;CO&mdash;Y, where R is an alkyl group having 6-20 carbons; Z is a radical selected from &mdash;CH &mdash;, &mdash;O&mdash;, and &mdash;NH&mdash;, two of these radicals coupled together, or &mdash;CH &boxH;CH &mdash;; Y is &mdash;NH , O&mdash;CH &mdash;C H , &mdash;CO&mdash;CO&mdash;O&mdash;CH , or O&mdash;CH ; and n is 1 or 2. It has been discovered that these compounds inhibit growth of microbial cells which synthesize &agr;-substitued, &bgr;-hydroxy fatty acids, particularly corynemycolic acid, nocardic acid, and mycolic acid. These compounds may be used to inhibit growth of mycobacterial cells, such as drug-resistant and

Inhibition of fatty acid synthase as a means to reduce adipocyte mass

Novel compounds for use in inhibiting fatty acid synthesis are disclosed. The compounds can be used for the treatment of tumors or microbial infections.

Growing community of inventors

Baltimore, MD, United States of America

Craig Arthur Townsend