The University of North Carolina at Chapel Hill

Cadus Technologies, Inc.

Other

Cadus Pharmaceutical Corp.

Cytogen Corporation

Princeton University

Karo Bio Ab

Imclone Systems, Inc.

Dana M Fowlkes

Brian K Kay

Joshua Trueheart

John P Manfredi

Christine A Klein

Jeremy I Paul

Andrew J Murphy

Andrew B Sparks

James R Broach

Jim Broach

Andrew J M Murphy

Stephen J McConnell

Noah Hoffman

Nils B Adey

Channing J Der

Charles T Tackney

Judith M Thorn

Lawrence A Quilliam

James E Rider

Gregorio Pirozzi

John N Snouwaert

Susan M Skelly

Robin Parish Hyde-Deruyscher

Jeffrey A Frelinger

Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of &#x3b1;-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

Yeast cells engineered to produce pheromone system protein surrogates, and uses therefor

The present invention pertains to novel yeast cells which are useful for the expression of heterologous G protein coupled receptors. The yeast cells of the present invention can be used in screening assays which can be used to screen for modulators of G protein coupled receptors. Specifically, the invention provides novel yeast cells which express a heterologous G protein coupled receptor and mutant and/or chimeric G protein subunit molecules which serve to functionally integrate the heterologous into the pheromone signaling pathway of the yeast cell. The invention also provides for the expression of heterologous G protein coupled receptors which are functionally integrated into the yeast cell membrane using a yeast &#x3b1; factor leader sequence. Drug discovery assays using the subject yeast cells are also provided.

Yeast cells expressing modified G proteins and methods of use therefor

Novel polypeptides having WW domains of interest are described, along with DNA sequences that encode the same. A method of identifying these polypeptides by means of a sequence-independent (that is, independent of the primary sequence of the polypeptide sought), recognition unit-based functional screen is also disclosed. Various applications of the method and of the polypeptides identified are described, including their use in assay kits for drug discovery, modification, and refinement.

Identification and isolation of novel polypeptides having WW domains and methods of using same

The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

Methods and compositions for identifying receptor effectors

Novel polypeptides having functional domains of interest are described, along with DNA sequences that encode the same. A method of identifying these polypeptides by means of a sequence-independent (that is, independent of the primary sequence of the polypeptide sought), recognition unit-based functional screen is also disclosed. Various applications of the method and of the polypeptides identified are described, including their use in assay kits for drug discovery, modification, and refinement.

Polypeptides having a functional domain of interest and methods of identifying and using same

Yeast cells engineered to produce pheromone system protein surrogates and uses therefor

Identification of drug complementary combinatorial libraries

Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins having an SH3 domain and glutathione S-transferase (GST). Preferred peptides are disclosed which comprise a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.

Nck SH3 binding peptides

The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a yeast expression library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

Methods for identifying G protein coupled receptor effectors

Growing community of inventors

Chapel Hill, NC, United States of America

Dana M Fowlkes