Self-Assembly, Antimicrobial Activity, and Membrane Interactions of Arginine-Capped Peptide Bola-Amphiphiles

Abstract

The self-assembly and antimicrobial activity of two novel arginine-capped bola-amphiphile peptides, namely RA6R and RA9R (R, arginine; A, alanine) are investigated. RA6R does not self-assemble in water due to its high solubility, but RA9R self-assembles above a critical aggregation concentration into ordered nanofibers due to the high hydrophobicity of the A9block. The structure of the RA9R nanofibers is studied by cryogenic transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Circular dichroism spectroscopy shows that both RA6R and RA9R adopt coil conformations in water at low concentration, but only RA9R adopts a β-sheet conformation at high concentration. SAXS and differential scanning calorimetry are used to study RA6R and RA9R interactions with a mixed lipid membrane that models a bacterial cell wall, consisting of multilamellar 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine vesicles. Cytotoxicity studies show that RA6R is more cytocompatible than RA9R. RA6R has enhanced activity against the Gram-negative pathogen P. aeruginosa at a concentration where viability of mammalian cells is retained. RA9R has little antimicrobial activity, independently of concentration. Our results highlight the influence of the interplay between relative charge and hydrophobicity on the self-assembly, cytocompatibility, and bioactivity of peptide bola-amphiphiles.

Peptide-Based Gel in Environmental Remediation: Removal of Toxic Organic Dyes and Hazardous Pb2+ and Cd2+ Ions from Wastewater and Oil Spill Recovery

“…Supramolecular gels [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] consisting of a variety of small organic molecules have attracted researchers' attention in the last few decades due to their various applications in chemical, material and biological sciences. [17][18][19][20] Among low molecular weight gelators, peptide amphiphilesbelong to a special category, because they provide a distinctive opportunity to design soft materials with controllable structural features and specific secondary structures.…”

Nanostructured Antimicrobial Peptides: Crucial Steps of Overcoming the Bottleneck for Clinics

“…Beyond the layout of X m Z n , peptide bola-amphiphiles are another class of surfactant-like peptides, which incorporate a hydrophilic group at either end of the relatively long hydrophobic chain ( Edwards-Gayle et al, 2019 ). The double-head of bola amphiphiles leads to the increase in solubility and the possibility of forming obvious external hydrophilic surfaces ( Fuhrhop and Wang, 2004 ).…”

“…Thus, compared with A 6 R and A 9 R, which can form nanostructures, only RA 9 R self-assembles into ordered nanofibers. Unlike the A m R series, RA 9 R has little antimicrobial activity and weaker cytocompatibility than RA 6 R and RA 3 R. Different from the A m R series SLPs, the increased length of hydrophobic tail of bola amphiphiles does not have a positive correlation with the improved antimicrobial activity and self-assembly propensity ( Edwards-Gayle et al, 2019 ).…”

Эволюционное Развитие И Структурное Разнообразие Природных Антимикробных Пептидов, Пептидомиметиков И Катионных Амфифилов На Основе Аминокислот

“…4, тип IV). Они могут проявлять не только самостоятельную антибактериальную активность [50], но и формировать эффективные наноразмерные транспортные системы доставки антисмысловых олигонуклеотидов. Подобные «боласомы» -антибактериальные комплексы предложено использовать при лечении заболеваний, вызванных патогенными грамположительными спорообразующими анаэробными бактериями Clostridium difficile [51], и в других вариантах терапевтической биотехнологии [52,53].…”