conjugation of constrained peptides for cancer diagnostics

癌细胞中离子通道的上调通常导致预后不良和转移增加。因此，确定这些离子通道的新调节剂将是非常有趣的，因为它将使我们能够描述这些事件中离子通道的功能和分子机制。此外，这些新的离子通道调节剂可能导致新的诊断工具和潜在的抗癌治疗的发展。为了开展这项研究，我们将利用高通量荧光筛选平台，结合详细的电生理分析，从粗毒液和天然产物提取物中识别和表征新型肽离子通道调节剂。这些新型调节剂将被测序，化学或重组生产，他们的详细活性评估和他们的结构确定使用核磁共振。这些多肽通常富含二硫化物，在血浆中非常稳定。然而，为了避免潜在的二硫化物键混乱，我们将开发方法，以纳入替代共价键，而不是二硫化物键。我们还将开发富含二硫化物的兼容共轭策略，以便能够标记这些离子通道调节剂，用于诊断探针的开发。

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.