Apamin is an 18-amino-acid, disulfide-rich peptide originally identified in honeybee (Apis mellifera) venom. It is widely used as a potent pharmacological probe for small-conductance Ca²⁺-activated K⁺ channels (KCa2/SK channels), particularly KCa2.2/SK2, and is commonly applied in ion-channel research, electrophysiology, neuroscience, and calcium-dependent signaling studies.

The mature peptide contains two intramolecular disulfide bonds and a C-terminal amide, structural features that are important for maintaining its compact bioactive conformation. For synthetic Apamin, peptide identity, correct disulfide connectivity, terminal modification, and analytical purity should therefore be considered together rather than relying on HPLC purity alone.

Apamin Product Information

Product Overview

Apamin is one of the best-characterized peptide inhibitors of the KCa2 family of small-conductance calcium-activated potassium channels, historically referred to as SK channels.

These channels couple intracellular Ca²⁺ signaling to membrane potassium conductance and contribute to the regulation of neuronal excitability and afterhyperpolarization. Because Apamin blocks KCa2 channels at very low concentrations, it is widely used as a pharmacological tool for distinguishing SK-channel-mediated currents from other potassium-channel activities.

Apamin should not be considered simply as an 18-residue linear peptide. Its biological activity depends on a compact structure stabilized by two native disulfide bridges. Disruption of the native disulfide architecture can substantially reduce or abolish biological activity.

Alan Scientific Technical View: For disulfide-rich bioactive peptides such as Apamin, a high HPLC purity value alone does not fully define product quality. Correct molecular mass, terminal modification, oxidation state, and disulfide connectivity are also important considerations when evaluating the final synthetic peptide.

Biological Activity & Target

Apamin is a potent inhibitor of small-conductance Ca²⁺-activated K⁺ channels and shows particularly strong activity toward KCa2.2 / KCNN2 / SK2.

Reported literature values vary according to species, expression system, and assay conditions.

These values should be interpreted as literature-reported ranges rather than universal experimental specifications.

The high sensitivity of KCa2.2/SK2 to Apamin is one reason the peptide is widely used for functional characterization of SK-channel activity.

Research Applications

Structural Features of Apamin

Apamin contains four cysteine residues forming two intramolecular disulfide bonds:

Cys1–Cys11

Cys3–Cys15

Its mature peptide sequence is:

CNCKAPETALCARRCQQH-NH₂

The peptide is also amidated at the C-terminus.

These structural constraints stabilize the compact conformation associated with Apamin activity. Classical folding studies have demonstrated cooperative formation of the native two-disulfide structure, illustrating the importance of oxidative folding in producing the intended bioactive peptide.

For synthetic Apamin, peptide-chain assembly is therefore only one part of production. Formation of the correct disulfide topology is an additional critical step in obtaining the intended molecular structure.

Sequence Features Relevant to Biological Activity

Apamin activity depends on both its disulfide-constrained structure and specific amino-acid residues within the mature sequence.

Structure–activity studies have highlighted the importance of positively charged residues in the C-terminal region, particularly Arg13 and Arg14, while disruption of the native disulfide bonds significantly affects biological activity.

This combination of:

disulfide-constrained structure, defined charged residues, and C-terminal amidation

helps explain why relatively small sequence or structural modifications can produce substantial changes in Apamin activity.

For analog development, substitutions should therefore be evaluated in the context of the complete folded peptide rather than by amino-acid identity alone.

Considerations for Synthetic Apamin

Apamin presents a more complex synthesis problem than a conventional linear research peptide.

The peptide chain can be assembled using standard peptide synthesis chemistry, but the four cysteine residues must subsequently form the intended two-disulfide topology.

For disulfide-rich peptides, analytical purity should therefore be interpreted together with structural and mass-based quality attributes.

Quality Control

Alan Scientific catalog peptides are supplied with analytical quality documentation appropriate to the selected product specification.

Peptide identity and purity are typically evaluated using:

Mass Spectrometry (MS) for molecular identity

and

Analytical HPLC for chromatographic purity.

A Certificate of Analysis (COA) is provided for the supplied batch according to the applicable product specification.

For disulfide-rich peptides such as Apamin, the expected oxidation state and molecular mass should also be considered when interpreting QC data.

Storage & Handling

Apamin should be handled as a research peptide and protected from unnecessary exposure to moisture and repeated temperature cycling.

For long-term storage, follow the batch-specific COA or product storage specification supplied with the material.

After reconstitution, peptide stability can depend on solvent composition, concentration, pH, temperature, and experimental conditions. Preparing appropriately sized aliquots can help minimize repeated freeze–thaw cycles.

Related Technical Resources

Custom Peptide Synthesis

Peptide Synthesis Overview

Peptide Modifications & Applications

Peptide Purification & Quality Control

Selected References

1. UniProtKB P01500 – Apamin, Apis mellifera.
Reviewed protein record describing Apamin as a selective KCa2 channel toxin and summarizing reported activity against KCa2.1, KCa2.2, and KCa2.3 channels.

2. Huyghues-Despointes BM, Nelson JW. Stabilities of disulfide bond intermediates in the folding of apamin. Biochemistry. 1992;31(5):1476–1483.
Describes the native disulfide architecture and folding behavior of Apamin.

3. Huyghues-Despointes BM, Nelson JW. Cooperative disulfide bond formation in apamin.
Examines cooperative formation of the native two-disulfide structure during peptide folding.

4. Structure-function relationships and site of action of apamin.
Classical structure–activity work examining the contribution of disulfide bonds and individual residues to Apamin activity.

5. Small conductance Ca²⁺-activated K⁺ channels as targets of CNS drug development.
Reviews SK-channel pharmacology and the use of Apamin as a functional research probe.

Why Source Research Peptides from Alan Scientific?

Alan Scientific provides catalog and custom research peptides supported by peptide synthesis expertise, analytical QC, and flexible modification capabilities.

For research programs involving Apamin analogs or related toxin-derived peptides, sequence, purity, quantity, terminal modification, salt form, and additional peptide modifications can be discussed according to project requirements.

Research Use Only