1.D.63 The Peptide-based Nanopore (PepNP) Family 

Re-engineering nature's molecules provides a strategy to obtain nanopores. Lella and Mahalakshmi 2016 reported a peptide engineering strategy through sequence reversal, which was applied onto the first transmembrane peptide of a mycobacteriophage membranoporin protein holin. They redesigned the membrane rupture property of this peptide to form nanopore ion channels with specific properties. The structural characterization and electrophysiology properties of a library of 28 engineered peptides with differing ion channel behaviors was reported. They identified key residues, charge distributions, and hydropathy indices of the peptides that contribute to the channel characteristics.

Mahendran 2021 developed a synthetic transmembrane peptide pore built entirely of short synthetic alpha-helical peptides. The formation of a stable uniform ion-selective pore with single-channel electrical recordings was developed. Cyclodextrins blocked the peptide pores. The kinetics of cyclodextrin binding and translocation were determined (Mahendran 2021). The diameters, stabilities, and membrane affinities of peptide pores by DNA-programmed self-assembly have been tuned (Fennouri et al. 2021). De-insertion current analysis of pore-forming peptides and proteins has been reviewed (Shoji 2022).



Fennouri, A., J. List, J. Ducrey, J. Dupasquier, V. Sukyte, S.F. Mayer, R.D. Vargas, L. Pascual Fernandez, F. Bertani, S. Rodriguez Gonzalo, J. Yang, and M. Mayer. (2021). Tuning the Diameter, Stability, and Membrane Affinity of Peptide Pores by DNA-Programmed Self-Assembly. ACS Nano. [Epub: Ahead of Print]

Lella, M. and R. Mahalakshmi. (2016). Engineering a Transmembrane Nanopore Ion Channel from a Membrane Breaker Peptide. J Phys Chem Lett 2298-2303. [Epub: Ahead of Print]

Mahendran, K.R. (2021). Building Synthetic Transmembrane Peptide Pores. Methods Mol Biol 2186: 19-32.

Shoji, K. (2022). De-Insertion Current Analysis of Pore-Forming Peptides and Proteins Using Gold Electrode-Supported Lipid Bilayer. Methods Mol Biol 2402: 93-102.