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Sci Rep ; 8(1): 14739, 2018 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-30282983

RESUMEN

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 Ca2+ channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca2+ 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 Ca2+ 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 peptide14-39 lacking pharmacological activity which was directed to the nucleus of specific cancer cell lines. This research identifies a novel subfamily of Ca2+ active toxins and provides new insights into biotechnological applications of animal venoms.


Asunto(s)
Calcio/química , Péptidos de Penetración Celular/química , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Secuencia de Aminoácidos/genética , Animales , Canales de Calcio , Línea Celular Tumoral , Péptidos de Penetración Celular/genética , Péptidos de Penetración Celular/farmacología , Péptidos de Penetración Celular/uso terapéutico , Citoplasma/efectos de los fármacos , Humanos , Venenos de Escorpión/química , Escorpiones/química
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