Premium
The Role of Terminal Functionality in the Membrane and Antibacterial Activity of Peptaibol‐Mimetic Aib Foldamers
Author(s) -
Adam Catherine,
Peters Anna D.,
Lizio M. Giovanna,
Whitehead George F. S.,
Diemer Vincent,
Cooper James A.,
Cockroft Scott L.,
Clayden Jonathan,
Webb Simon J.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705299
Subject(s) - chemistry , antibacterial activity , vesicle , membrane , peptide , bilayer , azide , stereochemistry , amino acid , organic chemistry , biochemistry , bacteria , genetics , biology
Peptaibols are peptide antibiotics that typically feature an N‐terminal acetyl cap, a C‐terminal aminoalcohol, and a high proportion of α‐aminoisobutyric acid (Aib) residues. To establish how each feature might affect the membrane‐activity of peptaibols, biomimetic Aib foldamers with different lengths and terminal groups were synthesised. Vesicle assays showed that long foldamers (eleven Aib residues) with hydrophobic termini had the highest ionophoric activity. C‐terminal acids or primary amides inhibited activity, while replacement of an N‐terminal acetyl with an azide group made little difference. Crystallography showed that N 3 Aib 11 CH 2 OTIPS folded into a 3 10 helix 2.91 nm long, which is close to the bilayer hydrophobic width. Planar bilayer conductance assays showed discrete ion channels only for N ‐acetylated foldamers. However long foldamers with hydrophobic termini had the highest antibacterial activity, indicating that ionophoric activity in vesicles was a better indicator of antibacterial activity than the observation of discrete ion channels.