Purification and biochemical characterisation of a putative sodium channel agonist secreted from the South African Knobbly sea anemone Bunodosoma capense
van Losenoord, W.; Krause, J.; Parker-Nance, S.; Krause, R.; Stoychev, S.; Frost, C.L. (2019). Purification and biochemical characterisation of a putative sodium channel agonist secreted from the South African Knobbly sea anemone Bunodosoma capense. Toxicon 168: 147-157. https://dx.doi.org/10.1016/j.toxicon.2019.06.222
In: Toxicon. Elsevier: Oxford. ISSN 0041-0101; e-ISSN 1879-3150, meer
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| Author keywords |
Nav channels; Artemia bioassay; Neurotoxin; Anthozoa; ß-defensin; Sea anemone |
| Auteurs | | Top |
- van Losenoord, W.
- Krause, J.
- Parker-Nance, S.
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- Krause, R.
- Stoychev, S.
- Frost, C.L.
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| Abstract |
Voltage gated ion channels have become a subject of investigation as possible pharmaceutical targets. Research has linked the activity of ion channels directly to anti-inflammatory pathways, energy homeostasis, cancer proliferation and painful diabetic neuropathy. Sea anemones secrete a diverse array of bioactive compounds including potassium and sodium channel toxins. A putative novel sodium channel agonist (molecular mass of 4619.7 Da) with a predicted sequence: CLCNSDGPSV RGNTLSGILW LAGCPSGWHN CKKHKPTIGW CCK was isolated from Bunodosoma capense using a modified stimulation technique to induce the secretion of the neurotoxin rich mucus confirmed by an Artemia nauplii bio-assay. The peptide purification combined size-exclusion and reverse-phase high performance liquid chromatography. A thallium-based ion flux assay confirmed the presence of a sodium channel agonist/inhibitor and purity was determined using a modified tricine SDS-PAGE system. The peptide isolated indicated the presence of multiple disulfide bonds in a tight β-defensin cystine conformation. An IC50 value of 26 nM was determined for total channel inhibition on MCF-7 cells. The unique putative sodium channel agonist initiating with a cystine bond indicates a divergent evolution to those previously isolated from Bunodosoma species. |
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