Antibacterial Activities of Short Designer Peptides: a Link between Propensity for Nanostructuring and Capacity for Membrane Destabilization

Abstract

Amphiphilic peptides A(3)K, A(6)K, and A(9)K displayed an increasing propensity for nanoaggregation with increasing the size of hydrophobic alanine moiety, and the size and shape of the aggregates showed a steady transition from loose peptide stacks formed by A(3)K, long nanofibers by A(6)K, to short and narrow nanorods by A(9)K. This size and shape transition was broadly consistent with the trend predicted from interfacial packing and curvature change if these peptide surfactants were treated as conventional surfactants. The antibacterial capacity, defined by the killing of percentage of bacteria in a given time and peptide concentration, showed a strong correlation to peptide hydrophobicity, evident from both microscopic and fluorescence imaging studies. For A(9)K, the power for membrane permeation and bacterial clustering intensified with peptide concentration and incubation time. These results thus depict a positive correlation between the propensity for self-assembly of the peptides, their membrane penetration power, and bactericidal capacity. Although the exposure of A(9)K to a preformed DPPC membrane bilayer showed little structural disturbance, the same treatment to the preformed DPPG membrane bilayer led to substantial disruption of model membrane structure, a trend entirely consistent with the high selectivity observed from membrane hemolytic studies.

Redox modulated hydrogelation of a self-assembling short peptide amphiphile

“…As shown in Figure 1, the N-and C-termini of the peptides were acetylated and amidated, respectively, to eliminate the effect of terminal charges that are believed to complicate the process of selfassembly. The detailed procedures have been described in our previous work [30][31][32][33]. Deprotection, activation, coupling and capping were carried out on the synthesizer and cleavage from the resin was finished manually away from the synthesizer.…”

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

“…Several earlier studies focused on their application as surfactants in membrane protein stabilization [18][19][20][21][22][23]. Their use as antimicrobial agents has also been considered [24,25]. Recently, peptide vesicles were tested for their capability as drug-or gene-delivery systems [26][27][28][29] or as bioactive scaffolds in tissue engineering applications [30][31][32].…”

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

“…Recently, researchers have claimed that short peptides have the ability to self-assemble into many different nanostructures that can minimize the difficulty and cost of the fabrication process and simultaneously enhance the stability [35,36]. Among them, dipeptide self-assembled nanostructures are investigated intensively for various biomedical applications including drug delivery.…”