Novel Design of Heptad Amphiphiles To Enhance Cell Selectivity, Salt Resistance, Antibiofilm Properties and Their Membrane-Disruptive Mechanism.

Abstract

Coiled-coil, a basic folding pattern of native proteins, was previously demonstrated to be associated with the specific spatial recognition, association, and dissociation of proteins and can be used to perfect engineering peptide model. Thus, in this study, a series of amphiphiles composed of heptads repeats with coiled-coil structures was constructed, and the designed peptides exhibited a broad spectrum of antimicrobial activities. Circular dichroism and biological assays showed that the heptad repeats and length of the linker between the heptads largely influenced the amphiphile's helical propensity and cell selectivity. The engineered amphiphiles were also found to efficiently reduce sessile P. aeruginosa biofilm biomass, neutralize endotoxins, inhibit the inflammatory response, and remain active under physiological salt concentrations. In summary, these findings are helpful for short AMP design with a highly therapeutic index to treat bacteria-induced infection.

• Authors: Xiujing Dou, Xin Zhu, Jiajun Wang, Na Dong, Anshan Shan
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 60 Issue 6 Pg. 2257-2270 (03 23 2017) ISSN: 1520-4804 [Electronic] United States
• PMID: 28230992 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Peptides
• Surface-Active Agents

Topics

• Amino Acid Sequence
• Anti-Bacterial Agents (chemistry, pharmacology)
• Bacteria (drug effects)
• Bacterial Infections (drug therapy, microbiology)
• Biofilms (drug effects)
• Circular Dichroism
• Drug Design
• Hemolysis (drug effects)
• Humans
• Models, Molecular
• Peptides (chemistry, pharmacology)
• Protein Structure, Secondary
• Pseudomonas Infections (drug therapy, microbiology)
• Pseudomonas aeruginosa (drug effects, physiology)
• Surface-Active Agents (chemistry, pharmacology)