CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells

Scorpion sting envenoming impacts millions of people worldwide, with cardiac effects being one of the main causes of death on victims. Here we describe the first Ca 2+ channel toxin present in Tityus serrulatus ( Ts ) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca 2+ release through the activation of nuclear InsP3R of cardiomyocytes, thereby causing an increase in the contraction frequency of these cells. Besides proposing a novel subfamily of Ca 2+ active toxins, we investigated its potential use as a drug delivery system targeting cancer cell nucleus using CPP-Ts’s nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts sub peptide 14–39 lacking pharmacological activity which was directed to the nucleus of specific cancer cell lines. This research identifies a novel subfamily of Ca 2+ active toxins and provides new insights into biotechnological applications of animal venoms.