Click (AAKK)4 – Click Peptides

Small peptide design has become of interest to catalyse chemical transformations within the cell. The aim is to generate peptides to enhance the hybridization of attached oligonucleotides to complementary DNA sequences. (AAKK)4 is modelled on the surface of staphylococcal nuclease, it a short cationic lysine-rich peptide that can deliver a nucleophile to DNA or RNA. (AAKK)4 peptide can improve DNA-PNA (peptide nucleic acid) hybridisations dramatically as well as increase strand invasion rate. (AAKK)4 peptide is a non-lipid approach for cell penetration which is preferable for certain cell lines due to cytotoxicity issues. (AAKK)4-antisense conjugates have been used to silence gene expression. (AAKK)4 is provided here with a N-terminal alkyne attachment. Two of the most regularly encountered functional groups for click chemistry are azides and alkynes, and the azide-alkyne cycloaddition has become the most popular click reaction. The use of click chemistry with alkyne-(AAKK)4 allows a wide variety of applications particularly for conjugation, modification, and peptide design.