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1.D.117.  The Pore-forming Synthetic KIA Peptide (KIA) Family

KIA peptides are a series of designer-made cationic amphipathic alpha-helical antimicrobial peptides of different lengths, based on the repetitive sequence [KIAGKIA]. They can form toroidal pores in membranes, wherein the helices are aligned in a transmembrane orientation. Solid-state (15)N NMR has been used to differentiate between the surface-bound and transmembrane states (Strandberg et al. 2020). The pore-forming activity increases when the peptides carry a positive charge (Lys residue) at the N-terminus, compared to a hydrophobic Ile-Ala N-terminal motif. In contrast, a positive charge at the C-terminus gives lower membrane activity compared to C-terminal Ile-Ala. For peptides with otherwise identical sequences, a more than ten-fold difference in vesicle leakage can be observed, depending on which terminus carries the charge. This difference is attributed to a shift in the equilibrium between peptide helices oriented on the membrane surface and those inserted into the membrane in a pore-forming state. Strandberg et al. 2020 showed that the 3D hydrophobic moment can be used to predict which peptide sequences are more prone to forming pores and will thereby show higher membranolytic activities.

References associated with 1.D.117 family:

Strandberg, E., D. Bentz, P. Wadhwani, J. B├╝rck, and A.S. Ulrich. (2020). Terminal charges modulate the pore forming activity of cationic amphipathic helices. Biochim. Biophys. Acta. Biomembr 183243. [Epub: Ahead of Print] 32126225