Identification of Uptake Mechanism of Cell-Penetrating Peptides by their Polar Profile

In the recent years, so-called cell-penetrating peptides (CPPs) have been in constant study due to its ability to penetrate cell membranes. CCPs are characterized by a length of less than 60 amino acids, its highly cationic nature and by a positive net charge at neutral pH. For the CPPs either an endocytic or non-endocytic uptake mechanism has been identified. This work presents the computational polarity index method that is able to predict the uptake mechanism of CPPs with an accuracy of 72% in a double-blind test. This was achieved by reading the peptide sequence and measuring the polarity as one single physico-chemical property. The method was verified by extracting all peptides from the CPPsite database (April 21, 2014) and its efficiency was tested with seven specialized databases of peptides and proteins.