Recombinant Cell Penetrating Peptide Construct for Targeting Mildly Acidic pH

A novel cell penetrating peptide (CPP) nanocomplex was produced by fusing glutathione S-transferase (GST) with a short pH-dependent peptide sequence. The peptide sequence is composed of a pH-sensitive masking sequence of 10-mer histidine-glutamic acid ((HE)10) cooligomer, and a CPP, model amphipathic peptide (MAP), KLALKLALKALKAALKLA, linked with a pentaglycine ((G)5) linker. The fusion protein is highly pH-sensitive with minimal binding and uptake at physiological pH (~7.4) and high CPP-mediated binding and uptake at pH 6.6 and below. This nanocomplex could serve as a model to design drug delivery systems that can specifically target physiological environments with mildly acidic pH