The State University of New York

Health Research, Inc.

Roswell Park Cancer Institute

Steven C Pruitt

David G Hangauer

Lawrence Mielnicki

Carleton C Stewart

Tao Ji

Alexander Hastie

Madison Lee

The present invention relates to 1,4-disubstituted naphthalene scaffold compounds and other closely related scaffold compounds. The present invention also relates to combinatorial libraries of such compounds. In addition, the present invention relates to a method of identifying a protein-protein interaction antagonist. The method first involves providing a compound as described herein. Next, the compound is contacted with interacting proteins of a protein-protein interaction target complex, whereby the compound is allowed to compete with the interacting proteins. Then, the activity of the compound for inhibiting formation of the protein-protein interaction target complex is measured. Finally, the compound that inhibits formation of the protein-protein interaction target complex is identified as a protein-protein interaction antagonist. Also disclosed is a method for modulating a protein-protein interaction. The method involves contacting interacting proteins of a protein-protein interaction target with a compound as described herein, whereby the protein-protein interaction between the interacting proteins is modulated.

Protein-protein interaction antagonist screening libraries based upon 1,4-disubstituted naphthalenes and related scaffolds

The present invention provides a method for identifying a plurality of pairs of interacting proteins and plasmids for use in the method. The pair of plasmids is adapted for use in a modified two hybrid system wherein wherein each plasmid comprises a recombinase recognition site. The method comprises the steps of providing cDNAs encoding test polypeptides, inserting the cDNAs into the first and second plasmids, recombining the first and second plasmids to obtain recombined plasmids, isolating and digesting the recombined plasmids, ligating the restriction fragments to a universal adapter to provide a pool of digested fragments flanked by a universal adapter, selecting and amplifying desired sequences, forming concatamers from the amplified sequences, and sequencing the concatamers to determine the nucleotide sequences encoding a plurality of pairs of interacting proteins.

Methods for protein interaction determination

The present invention provides a method for screening of a large number of compounds for their ability to modulate the expression of genes. The method uses gene trap technology and comprises the steps of transfecting a population of cells with a gene-trap vector, sorting cells according to their level of fluorescence, distributing sorted cells into pools and expanding the pools to obtain a sufficient number of cells representing each trapped gene to permit distinction of the effect of a test compound over controls, exposing the cells to the test compounds and identifying compounds which alter the fluorescence distribution pattern of cells using FACS analysis.

High throughput assay for identification of gene expression modifiers

The present invention is directed to recombinant DNA vector molecules and uses therefor. More particularly, the present invention relates to the construction of recombinant vectors useful in the high frequency cloning of cDNA. The present invention also relates to vectors capable of directing the synthesis of single stranded cDNA and thereby permitting enrichment of specific sequences by hybridization/selection.

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Williamsville, NY, United States of America

Steven C Pruitt