Protein Kinase C (PKC) is a family of serine/threomine enzymes involved with directing receptor activated signaling events of cellular growth and differentiation. PKC alpha, a lipid and calcium dependent PKC isoform is important in normal cellular functions and as well as disease. We plan to explore and discover conformational probes specific to PKC alpha protein. Phage display peptide libraries will be employed as tools to explore the entire PKC alpha protein. The experiments will be performed in the absence and presence of substrates and lipid activators. The identity of the binding peptides will be determined by DNA sequencing and confirmed with synthetic peptides. In Phase II a high throughput screen will be developed using peptide and PKC alpha. Seven other PKC enzymes will be explored for selective molecular recognition sites and screens developed for drug discovery. PROPOSED COMMERCIAL APPLICATION: The work is directed toward identification of unique relevant binding sites on PKC alpha protein for therapeutic intervention. Technology improvements in assay design and screening throughput will rest in enhancement of the drug discovery process.
Thesaurus Terms: conformation, fluorescence polarization, molecular shape, nucleic acid probe, protein binding, protein kinase C enzyme activity, enzyme substrate, peptide chemical synthesis, synthetic peptide enzyme linked immunosorbent assay, nucleic acid sequence, peptide library
