The invention relates to compositions, methods and uses of inhibitors of binding between PKC and CD28, and modulating an undesirable or aberrant immune response, disorder or disease, an inflammatory response, disorder or disease, inflammation or an autoimmune response, disorder or disease. Compositions include inhibitors of binding between PKC and CD28, which include, among others, PKC, CD28 and Lck sequences, subsequences, variants and modified forms, and polymorphisms.

Described herein are novel fluorescent sensors for Diacyl Glycerol (DAG) and phosphatidylinositol 4,5-bisphosphate (PIP2) that are based on circularly permuted fluorescent proteins. These sensors use less visible spectrum than FRET-based sensors, produce robust changes in fluorescence, and can be combined with one another, or with other sensors, in a multiplex assay on standard fluorescent plate readers or live cell imaging systems.

A peptide composition is provided which specifically inhibits the ability of -protein kinase C (PKC) to phosphorylate pyruvate dehydrogenase kinase (PDK) under ischemic conditions. The peptide composition is useful for treating or reducing tissue damage resulting from ischemia and/or reperfusion.

Provided herein are fusion proteins engineered from a dysferlin C2 domain sequence linked to a sequence of a homologous fusion partner, vector constructs with cDNA encoding the fusion proteins and viral vectors with the vector constructs and a promoter to control expression thereof. Also provided are methods for treating a dysferlinopathy in a subject in need thereof, for suppressing pathogenic Ca.sup.2+ signaling in a dysferlinopathic muscle and for targeting proteins to triad junctions in skeletal muscles all utilizing at least the fusion proteins.

The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A therapeutic peptide composition comprises a carrier peptide and a cargo peptide. A carrier peptide is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The cargo peptide is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

The present disclosure provides components and systems for targeted protein degradation in cells (e.g., in plant cells). In particular, the present disclosure provides a protein containing the Leucine-Rich Repeat (LRR) and novel E3 ligase (NEL) domains of SspH1 for use with Homology Region 1b (HR1b) domain of human PKN1 for degrading target proteins.

The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A therapeutic peptide composition comprises a carrier peptide and a cargo peptide. A carrier peptide is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The cargo peptide is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

The present invention relates to an siRNA targeting PRK2, which is a hepatitis C virus therapeutic agent, and can be effectively used as a hepatitis C virus therapeutic agent since the systemic delivery into a living body, particularly liver cells, is possible through an siRNA targeting a host PRK2 gene, which shows an anti-HCV activity, or a lipid formulation thereof.