Study of synthetic peptides derived from the PKI55 protein, a protein kinase C modulator, in human neutrophils stimulated by the methyl ester derivative of the hydrophobic N‐formyl tripeptide for‐Met‐Leu‐Phe‐OH

摘要: Elucidation of the involvement protein kinase C subtypes in several diseases is an important challenge for future development new drug targets. We previously identified PKI55 protein, which acts as a modulator, establishing feedback loop inhibition. The able to penetrate cell membrane activated human T-lymphocytes and inhibit activity α, β1 β2 isoforms. present study aimed identify minimal amino acid sequence that enzyme kinase C. Peptides derived from both C- N-terminal sequences were synthesized initially assayed rat brain part entire maintained in vitro effects described PKI55, then active peptides tested on isoforms β1, β2, γ, δ, e ζ their specific inhibition properties. Specific have been associated with activation signal transduction pathways involved inflammatory responses. Thus, potential therapeutic role selected has studied polymorphonuclear leukocytes by methyl ester derivative hydrophobic N-formyl tripeptide for-Met-Leu-Phe-OH evaluate ability modulate chemotaxis, superoxide anion production lysozyme release. These studies shown only chemotactic function significantly inhibited these peptides, whereas release remain unaffected. Western blotting experiments also demonstrated selective reduction levels β1 isoform, was be leukocyte response.