Autocamtide-3 Derived Inhibitory Peptide(AC3-I); CaMKII Inhibitor, myristoylated

Product Name: Autocamtide-3 Derived Inhibitory Peptide(AC3-I); CaMKII Inhibitor, myristoylated

Sequence One Letter Code: Myr-KKALHRQEAVDAL

Sequence Three Letter Code: Myr-Lys-Lys-Ala-Leu-His-Arg-Gln-Glu-Ala-Val-Asp-Ala-Leu-OH

Chemical Formula:C78H137N21O20

Molecular Weight: 1689.2

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Cardiovascular Disease Research

Conjugation: Unconjugated

Code Nacres: NA.26

Application: This peptide is a myristoylated form of AC3-I, a selective and proteolytically stable inhibitor of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). AC3-I is derived from Autocamtide-3, a CaMKII substrate, with substitution of the Thr9 phosphorylation site to alanine to prevent catalytic turnover. N-terminal myristoylation enhances membrane association and cellular uptake, facilitating intracellular inhibition of CaMKII signaling. This inhibitor is widely used to dissect CaMKII-dependent pathways in neuronal plasticity, learning and memory, cardiac contractility, and calcium-mediated signal transduction. It is suitable for biochemical, cellular, and physiological studies examining kinase regulation and downstream signaling effects.

Current Research: Calcium signaling plays a central role in regulating numerous cellular processes, including neuronal communication, muscle contraction, and gene expression. Among the key mediators of calcium-dependent signaling is Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), a multifunctional serine/threonine kinase that integrates intracellular calcium signals into diverse biological responses. Because CaMKII is involved in processes ranging from synaptic plasticity and memory formation to cardiac contractility, understanding its regulatory mechanisms has become an important focus of modern biomedical research. To support mechanistic studies of this kinase, researchers frequently employ selective peptide inhibitors such as myristoylated AC3-I, a proteolytically stable derivative designed to block CaMKII activity within cells. CaMKII and Calcium-Dependent Signal Transduction CaMKII is activated when intracellular calcium levels rise and bind to calmodulin, forming a Ca²⁺/calmodulin complex that interacts with the kinase. This interaction relieves autoinhibition and allows CaMKII to phosphorylate a wide range of substrates involved in signal transduction. Once activated, CaMKII can undergo autophosphorylation, enabling it to remain partially active even after calcium levels decline. This property allows the enzyme to act as a molecular memory device that links transient calcium signals to longer-term cellular responses. The functional importance of CaMKII is especially evident in neuronal systems, where it regulates synaptic strength and contributes to long-term potentiation (LTP), a cellular mechanism underlying learning and memory. In the cardiovascular system, CaMKII modulates calcium handling in cardiomyocytes, influencing heart rhythm and contractile function. Dysregulation of CaMKII signaling has been associated with neurological disorders, cardiac arrhythmias, and heart failure, highlighting the importance of precise tools for studying this enzyme. Development of the AC3-I Peptide Inhibitor One of the most widely used inhibitors for studying CaMKII is AC3-I, a peptide derived from Autocamtide-3, a well-characterized CaMKII substrate. Autocamtide peptides were originally designed to mimic natural phosphorylation targets of CaMKII, making them valuable tools for investigating kinase activity. AC3-I was engineered by modifying the Autocamtide-3 sequence to function as an inhibitor rather than a substrate. Specifically, the Thr9 phosphorylation site was replaced with alanine, preventing the peptide from undergoing catalytic phosphorylation. This substitution transforms the peptide into a competitive inhibitor, allowing it to bind to the CaMKII catalytic site without being processed by the enzyme. As a result, AC3-I effectively blocks kinase activity while remaining resistant to enzymatic turnover. Another advantage of AC3-I is its proteolytic stability, which improves its performance in biological experiments. Peptide inhibitors can often be degraded rapidly in cellular environments, but modifications to AC3-I help preserve its integrity during biochemical and cellular studies. Myristoylation for Enhanced Cellular Uptake To improve intracellular delivery, AC3-I can be modified by N-terminal myristoylation, producing the myristoylated AC3-I variant. Myristoylation involves the attachment of a myristic acid lipid moiety to the N-terminus of the peptide. This hydrophobic modification promotes association with cellular membranes and facilitates uptake into cells. The lipid modification significantly enhances the peptide’s cell permeability, allowing it to function effectively in intact cells and tissues. Once inside the cell, myristoylated AC3-I can interact with CaMKII and inhibit its catalytic activity, making it particularly valuable for experiments that require direct manipulation of intracellular kinase signaling. Applications in Neuroscience Research In neuroscience, CaMKII plays a critical role in regulating synaptic plasticity, the ability of synapses to strengthen or weaken over time. This plasticity underlies many forms of learning and memory. Myristoylated AC3-I is frequently used to investigate how CaMKII activity influences neuronal signaling pathways and synaptic remodeling. For example, researchers have used the inhibitor to examine the role of CaMKII in long-term potentiation (LTP) within hippocampal neurons. By selectively blocking CaMKII activity, scientists can determine how this kinase contributes to the strengthening of synaptic connections during memory formation. Such experiments provide valuable insights into the molecular mechanisms underlying cognitive processes. Role in Cardiovascular and Calcium Signaling Studies Beyond the nervous system, CaMKII is a major regulator of cardiac calcium handling. In cardiomyocytes, CaMKII influences ion channels, calcium release from the sarcoplasmic reticulum, and excitation–contraction coupling. Abnormal CaMKII activity has been linked to arrhythmias and cardiac dysfunction, making it a key focus of cardiovascular research. Myristoylated AC3-I enables investigators to selectively inhibit CaMKII in cardiac cells, allowing detailed study of how the kinase affects contractility and calcium cycling. This approach helps clarify the molecular pathways that contribute to both normal heart function and disease states. A Versatile Tool for Kinase Research Because of its selectivity, stability, and cell permeability, myristoylated AC3-I has become a widely used reagent for dissecting CaMKII-dependent pathways. The peptide is suitable for a range of experimental settings, including biochemical assays, cultured cell studies, and physiological investigations in complex tissues. By enabling precise inhibition of CaMKII signaling, this peptide supports research into neuronal plasticity, cardiac physiology, and calcium-mediated signal transduction. As scientists continue to explore the diverse roles of CaMKII in health and disease, tools such as myristoylated AC3-I remain essential for unraveling the regulatory networks that govern kinase activity and downstream cellular responses.