Membrane permeabilizing activity of new polycationic peptides derived from Cry type protoxins

Some of natural antimicrobial polycationic peptides and their artificial analogs have been found to reveal pro‐apoptotic action against cancer cells and solid tumors, targeting mitochondria. The anticancer efficiency of artificial KLA peptides has been shown to strongly increase by their conjugation to the “tumor homing” or cell‐penetrating polyarginie peptides. In this work, we found that polycationic peptides derived from various Cry type protoxins, without or with conjugated polyarginine vectors, are also highly active in the potential‐dependent permeabilization of mitochondrial and plasma membranes. Membrane permeabilization was monitored by light dispersion changes as indicator of mitochondrial or red blood cell swelling. Mitochondrial NAD(P)H fluorescence and DisC3(5) fluorescence were measured as indicators of membrane potential changes. Most of the designed Cry protoxin‐derived peptides, as for example BTM‐P1 peptide (Lemeshko et al., J. Biol. Chem., 2005; Lemeshko et al., US patent 7,041,647, 2006; Lemeshko, Arch. Biochem. Biophys., 2010), showed significantly higher membrane permeabilizing activities than their analogs with the reverse sequences. The obtained results indicate a promising design of anticancer polycationic peptides on the basis of natural sequences of membrane permeabilizing fragments of Cry type protoxins. (Colciencias grant #111840820380, Colombia).