Abstract
Animal venoms represent a rich source of pharmacologically active peptides that interact with ion channels. However, a challenge to discovering drugs remains because of the slow pace at which venom peptides are discovered and refined. An efficient autocrine‐based high‐throughput selection system was developed to discover and refine venom peptides that target ion channels. The utility of this system was demonstrated by the discovery of novel Kv1.3 channel blockers from a natural venom peptide library that was formatted for autocrine‐based selection. We also engineered a Kv1.3 blocker peptide (ShK) derived from sea anemone to generate a subtype‐selective Kv1.3 blocker with a long half‐life in vivo.
Gift der Wahl: Cystein‐Knoten‐Peptide wurden in der Gift‐Datenbank ausfindig gemacht und genutzt, um eine Lentiviren‐Vektorbibliothek für die Autokrin‐basierte Selektion von Peptiden, die Ionenkanäle angreifen, aufzubauen. Die Wechselwirkung des an die Membran angehängten Gift‐Peptids mit dem Ionenkanal bewirkt die proteasevermittelte Freisetzung eines Transkriptionsfaktors (orange), der die Expression eines Reportergens (rot) auslöst.