Controlling Interactions of Cyclic Oligosaccharides with Hetero‐Oligomeric Nanopores: Kinetics of Binding and Release at the Single‐Molecule Level

Abstract Controlling the molecular interactions through protein nanopores is crucial for effectively detecting single molecules. Here, the development of a hetero‐oligomeric nanopore derived from Nocardia farcinica porin AB (NfpAB) is discussed for single‐molecule sensing of biopolymers. Using single‐channel recording, the interaction of cyclic oligosaccharides such as cationic cyclodextrins (CDs) of different symmetries and charges with NfpAB is measured. Studies of the transport kinetics of CDs reveal asymmetric geometry and charge distribution of NfpAB. The applied potential promotes the attachment of the cationic CDs to the negatively charged pore surface due to electrostatic interaction. Further, the attached CDs are released from the pore by reversing the applied potential in time‐resolved blockages. Release of CDs from the pore depends on its charge, size, and magnitude of the applied potential. The kinetics of CD attachment and release is controlled by fine‐tuning the applied potential demonstrating the successful molecular transport across these nanopores. It is suggested that such controlled molecular interactions with protein nanopores using organic templates can be useful for several applications in nanopore technology and single‐molecule chemistry.