Helical 1:1 α/Sulfono-γ-AA Heterogeneous Peptides with Antibacterial Activity
As one of the greatest threats facing in 21st century, antibiotic resistance is now a major public health concern. Host-defense peptides (HDPs) offer an alternative approach to combat emerging multidrug-resistant bacteria. It is known that helical HDPs such as magainin 2 and its analogs adopt cationic amphipathic conformations upon interaction with bacterial membranes, leading to membrane disruption and subsequent bacterial cell death. We have previously shown that amphipathic sulfono-γ-AApeptides could mimic magainin 2 and exhibit bactericidal activity. In this article, we demonstrate for the first time that amphipathic helical 1:1 α/sulfono-γ-AA heterogeneous peptides, in which regular amino acids and sulfono-γ-AApeptide building blocks are alternatively present in a 1:1 pattern, display potent antibacterial activity against both Gram-positive and Gram-negative bacterial pathogens. Small Angle X-ray Scattering (SAXS) suggests that the lead sequences adopt defined helical structures. The subsequent studies including 2 fluorescence microscopy and time-kill experiments indicate that these hybrid peptides exert antimicrobial activity by mimicking the mechanism of HDPs. Our findings may lead to the development of HDP-mimicking antimicrobial peptidomimetics that combat drug-resistant bacterial pathogens. In addition, our results also demonstrate the effective design of a new class of helical foldamer, which could be employed to interrogate other important biological targets such as protein-protein interactions in the future.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Science Foundation (NSF); National Institutes of Health (NIH)
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1390789
- Journal Information:
- Biomacromolecules, Vol. 17, Issue 5; ISSN 1525-7797
- Publisher:
- American Chemical Society
- Country of Publication:
- United States
- Language:
- English
Similar Records
Right-Handed Helical Foldamers Consisting of De Novo
A Peptide Derived from Phage Display Library Exhibits Antibacterial Activity against E. coli and Pseudomonas aeruginosa