Leland Stanford Junior University

Terrapin Technologies, Inc.

Telik, Inc.

Dorit Ron

Daria D Mochly-Rosen

Eugene W Napolitano

Lawrence M Kauvar

Anna Voronova

John W Patterson

Hugo O Villar

Nicki Vasquez

Nicki J Vasquez

Anna F Voronova

Gene Napolitano

The present invention relates to a polypeptide composition effective to alter the activity of a first protein that interacts with a second protein, where the second protein contains at least one WD-40 region. The polypeptides of the present invention typically have between 4 and 50 amino acids whose sequence is the same as a sequence of the same length in the WD-40 region of the second protein. The invention further includes a method of altering the activity of the above described first protein. In one embodiment of the invention the polypeptide composition is effective to alter the activity of a protein kinase C, where the protein kinase C interacts with a second protein, and the second protein contains at least one WD-40 region (e.g., RACK1).

WD-40 derived peptides and uses thereof

WD-40-derived peptides and uses thereof

Compounds having immunomodulating activity are identified using a methodology which employs TER14687, TER10311 and/or TER17210 as standards. The effect candidate compounds have on PKC-theta interaction with cognate binding proteins is measured and compared with the standards. The interaction can be measured by a variety of techniques, including assessing translocation of said PKC-theta or fragment. Kits containing the TER14687, TER10311 and/or TER17210 standards are disclosed. TER14687, TER10311 and/or TER17210 are useful in modulating the immune system in a subject by reducing T-cell activity. TER14687, TER10311, TER17210 are used as leads to develop other compounds having immunomodulating activity.

Methods to identify immunomodulators using cognate interaction of

Modulators of the immune system can be identified by determining the ability of candidate substances to affect the interaction of PKC-theta or a fragment thereof with its cognate. The interaction can be measured using binding of the cognate as an index, or can be measured using a physiological response.

Methods for assessing libraries of candidate modulators of intracellular signaling transmission pathways are described. The methods assess the ability of candidates from the library to inhibit the binding of peptides which represent participants in the signaling pathways as either a signal-generating protein or its cognate partner binding at a noncatalytic site. Specific peptides useful in this regard have been identified.

Rapid screening method for effectors of signal transduction

The present invention discloses that the fyn protein binds to the PKC-theta protein. Based on this observation, the present invention provides methods of identifying agents which can be used to modulate immune system activity by blocking fyn/PKC-theta binding and therapeutic methods using such agents.

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San Francisco, CA, United States of America

Dorit Ron