Prediction of the penetration efficiency of proapoptotic peptides by cell-penetrating peptides (CPP) and anticancer peptides (ACP) using bioinformatics frameworks

Cancer is a major cause of death worldwide, and despite advancements in treatment, no effective cure exists. Pro-apoptotic peptides have emerged as a promising alternative to conventional anticancer drugs. However, their clinical application faces challenges due to the cell membrane's hydrophobic barrier, limiting peptide access to intracellular targets. To overcome this obstacle, research suggests that conjugating with cell-penetrating peptides (CPPs) can improve intracellular transport. We propose a bioinformatics approach to evaluate the efficiency of four CPPs (TAT, R8, ATP 128, and Penetramax) for delivering pro-apoptotic sequences BIM, NOXA, BID, and BMF. We also used four anti-cancer peptides (LL37, Pexig, CLS001, and Magainin II) to enhance CPP potency. Our method resulted in the selection of 60 CppProAcp sequences with a high and average probability of absorption efficiency. We evaluated these peptides (CppProAcp) for transfer effect, stability, thermodynamic properties, aggregation potential, folding speed, backbone flexibility, and in vivo administration sensitivity, resulting in the identification of 20 promising structures. Based on our study, this bioinformatic workflow can be universally applied to any CPP-peptide conjugation scheme.