Mimicking helical antibacterial peptides with nonpeptidic folding oligomers.
Unnatural oligomeric scaffolds designed to adopt defined secondary structures (e.g., helices), while retaining the chemical diversity of amino acid side chains, are of practical value to elaborate functional mimetics of bioactive alpha-polypeptides. Enantiopure N,N'-linked oligoureas as short as seven residues long have been previously shown to fold into a stable helical structure, stabilized by 12- and 14-membered H-bonded rings. We now report that eight-residue oligoureas designed to mimic globally amphiphilic alpha-helical host-defense peptides are effective against both gram-negative and gram-positive bacteria (including methicillin-resistant Staphylococcus aureus [MRSA]) and exhibit selectivity for bacterial versus mammalian cells. Circular dichroism (CD) spectroscopy studies suggest enhanced helical propensity of oligoureas in the presence of phospholipid vesicles. The utility of this new class of nonpeptidic foldamers for biological applications is highlighted by high resistance to proteolytic degradation.
Violette
Aude
A
Immunologie et Chimie Thérapeutiques, UPR 9021 CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, F-67084 Strasbourg Cedex, France.
Fournel
Sylvie
S
Lamour
Karen
K
Chaloin
Olivier
O
Frisch
Benoit
B
Briand
Jean-Paul
JP
Monteil
Henri
H
Guichard
Gilles
G
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001704:Biopolymers; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D016106:Methicillin Resistance; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001704:Biopolymers; D010455:Peptides