Discovery of bioactive peptides targeting ion channels upregulated in cancer

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The up-regulation of ion channels in cancerous cells typically lead to poor prognosis and increased metastasis. Identifying novel modulators for these ion channel would therefore be of great interest as it would allow us to delineate the ion channels function and molecular mechanism during these events. In addition, these novel ion channel modulators may lead to the development of novel diagnostic tools and potential anti-cancer therapeutics. To pursue this research we will be utilizing a high-throughput fluorescence-based screening platform in combination with detailed electrophysiological assays to identify and characterise novel peptidic ion-channel modulators from crude venom and natural products extracts. These novel modulators will be sequenced, chemically or recombinantely produced, their detailed activity assessed and their structures determined using NMR. These peptides are typically disulfide-rich and very stable in plasma. However, in order to avoid potential disulfide-bond scrambling, we will develop methodology to incorporate alternative covalent bonds instead of disulfide bonds. We will also develop disulfide-rich compatible conjugation strategies to be able to label these ion channel modulators for development of diagnostic probes.