Princeton University

Michigan State University

Martin F Semmelhack

Bonnie L Bassler

Lark J Perez

Wai-Leung Ng

Shawn R Campagna

Colleen T O'Loughlin

Yigong Shi

Knut Drescher

Douglas A Higgins

Michiko E Taga

Christopher Waters

Frederick M Hughson

Diana Shi

Kristina M Kraml

George McLendon

Rachael A Kipp

Samuel Wang

Martin Case

Philip A Albiniak

Jianping Cong

Aislyn D Wist

Michael J Federle

Stephen T Miller

Albert Siryaporn

Karthik Sambanthamoorthy

Karina B Xavier

Matthew Neiditch

Laura C Conrad-Miller

Megan Eileen Bolitho

A structurally distinct and potent series of synthetic small molecule activators ofquorum sensing have been chemically synthesized. The small molecule activators reduce virulence in. Acyl pyrrole molecules displayed strong potency and stability, particularly 1-(1H-pyrrol-3-yl)decan-1-one.

Heterocycle analogs of CAI-1 as agonists of quorum sensing in vibrio

Antivirulence strategies to combat, are described. One strategy encompasses synthesis of a series of compounds that inhibit the production of pyocyanin, a redox-active virulence factor produced by this pathogen. A related strategy encompasses synthesis of compounds that inhibit the twoquorum-sensing receptors, LasR and RhlR, inhibit production of pyocyanin, and inhibit biofilm formation.

Molecules and compositions that inhibit gram negative bacteria and their uses

Double caged GABA compounds and compositions including the same are described. Methods of synthesizing and using double caged GABA compounds are provided.

Double caged GABA compounds, bis-CNB-GABA

Using a whole-cell high-throughput screen, eleven molecules were identified that activatequorum sensing (QS). Eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the globalQS cascade. Pro-QS molecules are used for the development of novel anti-infectives.

Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios

The various embodiments relate to a compound comprising: wherein R, R, R, R, R, R, R, R, R, R, R, and Rare each independently hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, alkoxy, aryloxy, heteroaryloxy, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, acyl, acylamino, amino, alkylamino, dialkylamino, arylamino, carboxylate (&#x2014;COH), cyano, nitro, &#x2014;CONH2, heteroarylamino, oxime, alkyloxime, aryloxime, amino-oxime or halogen when A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, and Q are carbon, and X is O, NR (where R is hydrogen, alkyl, aryl or acyl), S, SO (sulfoxide), SO(sulfone), or C(R)(where R=H, alkyl, aryl, alkenyl, alkynyl, or acyl); or wherein R, R, R, R, R, R, R, R, R, R, R, and Rare each independently hydrogen or hydroxyl when A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, and Q are each independently nitrogen, and compositions, combinations, pharmaceutically acceptable salts, esters, and prodrugs thereof. The invention also relates to methods of using such compounds and compositions.

Benzimidazole inhibition of biofilm formation

A bacterial autoinducer, CAI-1, was purified and its structure identified. Methods for synthesis of the autoinducer and its analogues were elucidated. Methods of using the autoinducer or its analogues for treating bacterial pathogenicity and bio film formation are described. Methods for prevention and treatment of cholera are described. Synthetic (S)-3-hydroxytridecan-4-one functions as well as natural CAI-1 in repressing production of the virulence factor toxin co-regulated pilus (TCP). Strategies are described to manipulate bacterial quorum sensing in the clinical arena.

Identification of bacterial autoinducer and use in treating bacterial pathogenicity

Compounds that bind cellular IAPs (inhibitor of apoptosis proteins) are disclosed. The compounds are mimetics of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABOLO, IIid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these compounds for therapeutic, diagnostic and assay purposes.

IAP binding compounds

This invention provides a practical synthesis route for 4,5-dihydroxypentane-2,3-dione (DPD), an unstable small molecule which is proposed to be the source of universal signaling agents for quorum sensing in bacteria. The synthesis route includes new intermediates and allows preparation of isotopically-labeled DPD and ent-DPD. The method provides sufficient quantities of DPD for study of spontaneous binding of borate to DPD, the signal for the marine bacteria

Expeditious synthesis of DPD

This invention relates to crystals comprising apo-LsrB and holo-LsrB. The structure of holo-LsrB identifies a tetrahydroxytetrahydrofuran derived from 4,5-dihydroxy-2,3-pentanedione (DPD) as the active autoinducer-2 (AI-2) molecule in. The X-ray crystallographic data can be used in a drug discovery method. Additionally the invention provides AI-2 analogs based on this discovery as well as pharmaceutical compositions containing those analogs.

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Princeton, NJ, United States of America

Martin F Semmelhack