Basic Design Elements for Tunable Cation Transport Using Picolinic-Acid-Incorporated Tetrapeptides

Selective transport of cations across cell membranes is essential for various biological functions in the body. Synthetic pores that mimic the selectivity of natural ion channels are attractive for development of drugs and materials. Peptides are now emerging as attractive therapeutic agents due to their biocompatibility and ready accessibility. Herein, we report a systematic study that identifies key elements to design cation-selective channels using tetrapeptide scaffolds. The scaffolds are derived from picolinic acid and alanine. Their ion transport activity is enhanced by hydrophobic long alkyl chains at the N-terminus. These scaffolds are exciting as cation-selectivity can be induced as well as switched by varying the oligoether groups at the C-terminus.