Deconstructing the potency and cell-line selectivity of membranolytic anticancer peptides

25 January 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Current cancer treatments damage healthy cells and tissues, causing short-term and long-term side effects. New treatments are desired that show greater selectivity toward cancer cells and evade the common mechanisms of multidrug resistance. Membranolytic anticancer peptides (mACPs) hold promise against cancer and multidrug resistance. The amphipathicity, hydrophobicity, and net charge of mACPs are all known to play a role in their respective interactions with cell membranes and the overall biological inhibition of cancer cells, but they are insufficient to explain their cell-line selectivity. To support the design of cell-line selective mACPs, we investigated the relationships that peptide features (amino acid composition, physicochemical properties, sequence motifs and sequence homology) could have with their potency and selectivity towards several healthy and cancer cell lines. Hydrophobicity, net charge and the presence of small and aliphatic residues influenced the potency and selectivity of mACPs across cancer cell lines in a cell-specific manner.

Keywords

Peptides
membranes
cancer
biological activity
potency
cell-line selectivity

Supplementary materials

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Description
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Supporting Information
Description
Contains additional figures and tables
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Lipid_composition_CCLs
Description
Tabulated lipid composition for specific cancer cell lines
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