Page - (000245) - in Biomedical Chemistry: Current Trends and Developments

(Lindgreen, 2006) YTA4 IAWVKAFIRKLRKGPLGa (Lindgreen, 2006) MMP cleavage site as seeding sequence M918 MVTVLFRRLRIRRACGPPRVRVa (El-Andaloussi, 2007) Tumor suppressor protein p14ARF CADY GLWRALWRLLRSLWRLLWRAb (Crombez, 2007) Derived from PPTG1 peptide, W and charged amino acids a C-terminal amide. b C-terminal cysteamide. Initially, CPPs were composed of only natural amino acids but recently have included non-primary and even unnatural amino acids (Farrera- Sinfreu, 2005). Furthermore, when lysine residues are replaced with ornithine residues, the peptide becomes more resistant to cellular degradation (Ezzat, 2011; Angeles-Boza, 2010). Cargo delivery efficiency can also be improved by changing the structure of the peptides, such as modification into dendrimers (Angeles-Boza, 2010; Bode, 2014), cyclic peptides (Mandal, 2011; Northfield, 2014), and the often-used strategy of modifying the side chains of CPPs, such as in TP10 derivatives (Andaloussi, 2011; Oskolkov, 2011). Recently, Vale’s research group developed new CPP-Gemcitabine conjugates for drug delivery in cancer therapy (Vale, 2016). Further investigations into the structure and mechanisms of uptake of CPP-cargo complexes will be required to evaluate CPPs as potential delivery tools for biomolecules in vitro and in vivo models. However, considering evidence from numerous studies, CPPs have the potential to become a universal tool to carry therapeutic molecules across cellular membranes without a risk of toxicity or inflammatory reactions.