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1.D.25 The Arylamine Foldamer (AAF) Family

Small arylamide foldamers, designed to mimic the amphiphilic nature of antimicrobial peptides, are bactericidal against both Gram-negative and Gram-positive bacteria (Mensa et al., 2011). These foldamers cause large changes in the permeability of the outer-membrane of Escherichia coli and more limited permeabilization of the inner membrane which reaches critical levels corresponding with the time required to bring about bacterial cell death. Transcriptional profiling of E. coli treated with sub-lethal concentrations of the arylamides showed induction of genes related to membrane and oxidative stresses, with some overlap to the effects observed for polymyxin B (Mensa et al., 2011). Protein secretion into the periplasm and the outer-membrane is also compromised, possibly contributing to the lethality of the arylamide compounds. The use of cell-penetrating peptide foldamers  as drug-delivery tools has been reviewed (Oba 2019), and more recently, foldamer-mediated transport across phospholipid bilayershas been reviewed (Zubair et al. 2024).  Foldamer transporters are described in TC families 1.D.25, 1.D.175, 1.D.225. and 1.D.281.

This family belongs to the: Artificial Foldamer (AF) Superfamily.

References associated with 1.D.25 family:

Mensa B., Kim YH., Choi S., Scott R., Caputo GA. and DeGrado WF. (2011). Antibacterial mechanism of action of arylamide foldamers. Antimicrob Agents Chemother. 55(11):5043-53. 21844313
Oba, M. (2019). Cell-Penetrating Peptide Foldamers: Drug-Delivery Tools. Chembiochem 20: 2041-2045. 30997711
Zubair, I., L. Martínez-Crespo, and S.J. Webb. (2024). Foldamer-mediated transport across phospholipid bilayers. Curr Opin Chem Biol 84: 102549. [Epub: Ahead of Print] 39616809