Large molecules & automated patch clamp

While automated patch clamp (APC) systems have been used for small molecule drug discovery and characterization for the past 20 years, the use of APC systems for large molecule characterization has lagged.

However, large molecules – and hence their characterization by APC – are becoming increasingly important in drug discovery. Currently, more than 90% of approved drugs are small molecules. Still, large molecules (>1 kDa, also known as biologics) are rapidly rising in prominence and importance in drug discovery and already constitute the lion’s share of the top 10 selling drugs worldwide.

Classes of large molecules

  • Venom, toxins and peptides (~3-4 kDa, 30-40 amino acids)
  • Wnt peptides (~35-45 kDa, 350-400 amino acids)
  • Knotbodies and nanobodies (~50-60 kDa, 400-500 amino acids)
  • Antibodies (~150-170 kDa, ~1400 amino acids)
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Sophion venom, toxins and peptides illustrations with Automated Patch Clamp

Venom, toxins and peptides

Animal and plant venoms have evolved as potent ion channel modulators to interfere with critical roles in physiological pathways, e.g. action potential initiation and propagation. Several toxins are highly potent and specific to individual ion channels. They have been widely used tools in research to elucidate the structure and function of ion channels. Increasingly, toxins have been used to develop novel therapeutics as peptide frameworks for new bioactive molecules or target scaffolds for drug conjugates.

To learn more about using automated patch clamp for venom and peptide characterization, look at the plethora of publications from the University of Queensland using QPatch. Also, you can watch the Sophion webinar on a venom toxin library screen using Qube 384.

Sophion Wnt peptides illustrations with Automated Patch Clamp

Wnt peptides

Wingless-related integration site (Wnt) comprises a diverse family of secreted signaling glycoproteins that are 350–400 amino acids in length and act as close-range signaling molecules. Wnt signal activation initiates a complex downstream signal cascade in eukaryotic cells and is critical in developing many diseases, including cancer. Wnt peptides activate K+ currents by elevating intracellular Ca2+ and triggering Ca2+ release from intracellular stores. Wnt peptides have significant implications for gene transcription and open novel avenues to modulate this critical pathway.

If you would like to learn more about using automated patch clamp for Wnt characterization, watching the Sophion webinar on ion channels in oncology with Kings College London is a great place to start. Also, check out the publications below:

Sophion knotbodies and nanobodies illustrations with Automated Patch Clamp

Knotbodies and nanobodies

Knotted peptides present a wealth of structurally diverse, biologically active molecules. The inhibitor cystine knot/knottin class is among the most ecologically common. Many of these natural products interact with extracellular targets, such as voltage-gated ion channels, with exquisite selectivity and potency, making them intriguing therapeutic modalities.

Learn more about using automated patch clamp for knotbodies and nanobodies; check out the posters from IONTAS on Generating ion channel-blocking antibodies by fusing knottin to peripheral CDR loops and Generating potent and selective inhibitors of Kv1.3 ion channels by fusing venom-derived mini proteins into peripheral CDR loops of antibodies.

Sophion antibodies illustrations with Automated Patch Clamp


Antibodies display high specificity, selectivity, and affinity for their target antigen, potentially precisely targeting ion channels. Nonetheless, isolating antibodies to ion channels is challenging. This is due to the difficulties in the expression and purification of ion channels in a format suitable for antibody drug discovery and due to the complexities of screening for function.

If you would like to learn more about using automated patch clamp for antibody characterization, please give us a call. We can share tips and tricks that will ensure you accurate results and good success rates. You can also read the publications below:

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