epsilon-V1-2, PKCe Inhibitor, Cys-conjugated

Product Name: epsilon-V1-2, PKCe Inhibitor, Cys-conjugated

Sequence One Letter Code: EAVSLKPTC

Sequence Three Letter Code: H-Glu-Ala-Val-Ser-Leu-Lys-Pro-Thr-Cys-OH

Chemical Formula:C40H70N10O14S1

Molecular Weight: 947.2

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Cardiovascular Disease Research

Source / Species: Human, mouse, rat, bovine

Conjugation: Unconjugated

Code Nacres: NA.26

Application: PKCε Inhibitory Peptide (εRACK Interaction Disruptor) is a selective peptide inhibitor that blocks protein kinase C epsilon (PKCε) signaling by disrupting its interaction with the anchoring protein εRACK (receptor for activated C kinase). By preventing PKCε translocation to specific cellular compartments, the peptide inhibits downstream phosphorylation events such as MARCKS phosphorylation, thereby modulating PKCε-dependent signaling pathways. A C-terminal cysteine residue enables site-specific conjugation to carrier proteins through disulfide bond formation, facilitating targeted delivery or experimental modification. This peptide is widely used to investigate PKCε-mediated signaling in cardiovascular biology, neuroprotection, ischemia–reperfusion injury, and cancer cell signaling, providing a valuable tool for dissecting PKC-dependent regulatory mechanisms.

Current Research: Protein kinase C (PKC) enzymes are a family of serine/threonine kinases that regulate numerous cellular processes, including signal transduction, cell survival, metabolism, and gene expression. Among the PKC isoforms, protein kinase C epsilon (PKCε) has attracted significant attention because of its roles in cardiovascular protection, neuronal signaling, and cancer biology. The PKCε inhibitory peptide, designed as an εRACK interaction disruptor, provides a selective approach to modulating PKCε signaling by preventing its association with its anchoring protein, εRACK (receptor for activated C kinase). This targeted mechanism makes the peptide a valuable experimental tool for studying PKCε-dependent signaling pathways in diverse biological systems. PKCε and Its Role in Cellular Signaling PKCε belongs to the novel PKC (nPKC) subfamily, which is activated by diacylglycerol but does not require calcium for activation. Like other PKC isoforms, PKCε regulates signaling pathways by phosphorylating downstream substrate proteins. Activation of PKCε typically involves translocation of the enzyme from the cytosol to specific cellular compartments, such as membranes or cytoskeletal structures. This spatial targeting is mediated by interactions with specialized scaffolding proteins known as RACKs (receptors for activated C kinases). For PKCε, the primary anchoring protein is εRACK, which directs the kinase to precise subcellular locations where it can phosphorylate specific substrates and participate in localized signaling events. Through these mechanisms, PKCε contributes to several important biological processes, including: Regulation of cardiac contractility and cardioprotection Modulation of neuronal survival and synaptic signaling Control of cell proliferation and migration Participation in stress response pathways Because PKCε signaling is highly compartmentalized, disrupting its interaction with anchoring proteins provides a way to selectively interfere with its activity. Mechanism of the PKCε Inhibitory Peptide The PKCε inhibitory peptide is designed to block the interaction between PKCε and εRACK. By mimicking or competing with the binding interface required for this interaction, the peptide prevents PKCε from associating with its anchoring partner. When the interaction is disrupted, PKCε cannot properly translocate to its functional sites within the cell. As a result, the kinase is unable to efficiently phosphorylate its downstream targets. One well-characterized PKC substrate affected by this inhibition is MARCKS (myristoylated alanine-rich C kinase substrate). MARCKS phosphorylation normally occurs following PKC activation and plays a role in cytoskeletal regulation and membrane signaling. By preventing PKCε localization, the inhibitory peptide suppresses PKCε-dependent phosphorylation events, including MARCKS modification. This selective mechanism allows researchers to study the role of PKCε in specific signaling pathways without broadly inhibiting other PKC isoforms. Structural Feature for Experimental Modification A notable feature of the PKCε inhibitory peptide is the presence of a C-terminal cysteine residue. This cysteine provides a reactive thiol group that enables site-specific conjugation to other molecules through disulfide bond formation. This capability allows the peptide to be linked to: Carrier proteins Cell-penetrating peptides Targeting ligands Experimental probes Such modifications can facilitate intracellular delivery, enhance stability, or enable specialized experimental applications. Applications in Cardiovascular Research PKCε signaling has been extensively studied in cardiovascular biology, particularly in the context of cardioprotection during ischemic stress. Activation of PKCε has been associated with protective signaling pathways that reduce damage during ischemia–reperfusion injury. Using the PKCε inhibitory peptide, researchers can examine how blocking PKCε signaling influences cardiac responses to stress. This approach has helped clarify the role of PKCε in pathways regulating mitochondrial function, oxidative stress responses, and cardiac survival mechanisms. Use in Neurobiology and Neuroprotection Studies PKCε is also involved in neuronal signaling and neuroprotective pathways. Studies have shown that PKCε activity influences synaptic plasticity, neuronal survival, and responses to cellular stress. The inhibitory peptide allows researchers to selectively suppress PKCε-mediated signaling in neuronal cells, enabling detailed investigation of how this kinase contributes to neuroprotection, synaptic regulation, and neuronal adaptation to injury. Applications in Cancer Signaling Research In cancer biology, PKCε has been implicated in pathways controlling cell proliferation, migration, and survival. Abnormal PKCε signaling has been observed in several tumor types, suggesting a role in tumor progression and metastasis. By disrupting PKCε–εRACK interactions, the inhibitory peptide enables researchers to examine how PKCε localization and activity influence cancer cell signaling networks. This approach helps identify pathways that may contribute to tumor growth and therapeutic resistance. A Tool for Dissecting PKCε-Dependent Mechanisms Selective inhibitors that target protein–protein interactions provide powerful tools for analyzing complex signaling pathways. The PKCε inhibitory peptide (εRACK interaction disruptor) offers a precise method for interfering with PKCε localization and activity. Through its ability to block PKCε translocation and downstream phosphorylation events, this peptide supports research into PKC-dependent regulatory mechanisms in cardiovascular biology, neuroprotection, ischemia–reperfusion injury, and cancer signaling. Its compatibility with targeted conjugation strategies further expands its utility as an experimental probe for studying kinase signaling pathways.