Abstract: The present application relates to K-Ras mutations, to polynucleotides encoding mutant K-Ras polypeptides, and to methods of identifying small molecule antagonists using K-Ras mutations. The present application also relates to K-Ras small molecule antagonists and use thereof in the treatment of tumors.

Abstract: The present invention comprises cell penetrating peptides that bind to interferon regulatory factor IRF5 and disrupt the IRF5 homo-dimerization and/or attenuate downstream signaling, and a method for screening peptides that inhibit IRF5. Generally, the cell penetrating peptides of the invention bind human interferon regulatory factor IRF5 (CPP-IRF5).

Abstract: The present invention provides a method for testing an agent for its ability to inhibit binding between fibroblast growth factor (FGF) and heparan sulfate, comprising the steps of: interacting in solution immobilized FGF on a solid support with the agent and labeled heparan sulfate, and detecting the presence or absence of label in the solution remote from the solid support.

Abstract: The present invention provides a method for testing an agent for its potential to inhibit heparanase catalytic activity, comprising the steps of: interacting immobilized heparanase substrate binding protein on a solid support with labeled heparanase substrate to provide immobilized labeled heparanase substrate, interacting a heparanase enzyme solution with the immobilized labeled heparanase substrate in the presence of the agent, and detecting the presence or absence of label in the solution remote from the solid support. The labeled heparanase substrate may be bound to an immobilization bridge which binds to immobilized molecules on a solid support, to provide bridge-immobilized labeled heparanase substrate.

Abstract: The present invention provides a method for testing an agent for its potential to inhibit heparanase catalytic activity, comprising the steps of: interacting immobilized heparanase substrate binding protein on a solid support with labeled heparanase substrate to provide immobilized labeled heparanase substrate, interacting a heparanase enzyme solution with the immobilized labeled heparanase substrate in the presence of the agent, and detecting the presence or absence of label in the solution remote from the solid support. The labeled heparanase substrate may be bound to an immobilization bridge which binds to immobilized molecules on a solid support, to provide bridge-immobilized labeled heparanase substrate.

Abstract: Protein-protein interactions represent a large and important group of drug targets involved in the development and progression of human diseases. However, their utilization in drug discovery has been hampered by the low probability of identifying small-molecule inhibitors able to disrupt protein binding with desirable potency and selectivity. Therefore, the capability for rapid screening of large compound libraries has been critical for the exploration of this target class. The present invention relates to a homogeneous time-resolved fluorescence assay for identification of inhibitors of Cks1-Skp2 binding that plays a critical role in the ubiquitin-dependent degradation of p27. The assay was implemented in a 1536-well format using the new Zeiss uHTS robot and achieved a throughput in excess of 100,000 data points per day. A protocol for a fully automated high throughput IC50 determination was developed for hit validation.

Abstract: The present invention provides a method for testing an agent for its potential to inhibit heparanase catalytic activity, comprising the steps of: interacting immobilized heparanase substrate binding protein on a solid support with labeled heparanase substrate to provide immobilized labeled heparanase substrate, interacting a heparanase enzyme solution with the immobilized labeled heparanase substrate in the presence of the agent, and detecting the presence or absence of label in the solution remote from the solid support. The labeled heparanase substrate may be bound to an immobilization bridge which binds to immobilized molecules on a solid support, to provide bridge-immobilized labeled heparanase substrate.

Abstract: The present invention involves the protein glycosyl-phosphatidyl-specific phospholipase D (GPI-PLD) in a substantially pure form, an isolated nucleotide sequence encoding GPI-PLD, vectors containing the isolated nucleotide sequence encoding GPI-PLD, and cells transformed by a vector containing the isolated nucleotide sequence encoding GPI-PLD, also nucleotide sequences, vectors and cells comprising hybrid genes with GPI-PLD, and methods for producing secreted proteins.

Abstract: DNA sequences, recombinant DNA molecules and hosts transformed with them which produce human lipocortin-like polypeptides and methods of making and using these products. The DNA sequences and recombinant DNA molecules are characterized in that they code on expression for a human lipocortin-like polypeptide. In appropriate hosts these DNA sequences permit the production of human lipocortin-like polypeptides useful as anti-inflammatory agents and methods in the treatment of arthritic, allergic, dermatologic, ophthalmic and collagen diseases as well as other disorders involving inflammatory processes.