Rapid Fire 9th Venoms to Drugs 2026

Venom peptide tracers for receptor imaging using modular signal amplification (#007)

Theresa Lehner 1 2 , Monika Persic-Böhm 1 , Harrison Madge 2 , Markus Muttenthaler 1 2
  1. Institute of Biological Chemistry, University of Vienna, Vienna, Austria
  2. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

Venom peptides have evolved exceptional affinity and selectivity toward proteins/receptors, making them attractive leads for the development of specific imaging probes.1 In this project, venom peptides are repurposed as fluorescent tracers for the visualisation of drug targets, including low-abundance receptors. Many of these targets remain difficult to study with conventional antibodies due to their limited tissue penetration and challenges in raising selective antibodies against membrane proteins.2

Our work focuses on nicotinic acetylcholine receptors and voltage-gated sodium channels, key targets in neuroinflammation, chronic pain and neurological disorders.1

The investigated peptide probes were based on the venom peptides RgIA, a disulfide-rich peptide from Conus regius, that antagonises the α9α10 nicotinic acetylcholine receptor, and also acts as a GABAB agonist, and the linear peptide Tα3α from Tetramorium africanum, a Nav1.7 gating modifier.3,4 Peptide analogues were synthesised and functionalised with modular reporter systems, including directly attached fluorophores and epitope and oligonucleotide tags.5 These strategies were designed to enhance fluorescence sensitivity while preserving the pharmacological properties of the peptide tracers. The probes were evaluated in cell lines expressing the respective targets using advanced widefield microscopy, in which direct fluorophore labelling was compared with antibody labelling and a nucleic acid-based amplification strategy with respect to signal intensity, signal-to-background ratio and assay robustness. Furthermore, the selected probes were pharmacologically assessed to confirm that chemical modifications did not compromise target recognition or biological activity.

By combining the intrinsic target selectivity of venom peptides with modular signal-amplification technologies, our work provided novel tools and approaches for studying receptor localisation and dynamics, thereby supporting investigations of receptor biology and venom-inspired translational research. The developed probes are expected to find applications in tissue microarrays, spatial profiling and fluorescence-assisted cell sorting, techniques that play central roles in cancer research, biomarker discovery and precision medicine.

  1. Bajaj S. et Han J. (2019) Front. Pharmacol., 10(58).
  2. Persic-Böhm, M. et al. (2025) Angew. Chem. Int. Ed., 64(46), e202515180.
  3. Muttenthaler, M. et al. (2020) Aust. J. Chem., 73(4), 327-333.
  4. Thapa A. et al. (2024) J. Biol. Chem. 300(10), 107757.
  5. Mohsen M. G. et Kool E. T. (2016) Acc. Chem. Res., 49(11), 2540–2550.