Dataset Information

Sono-Assembly of the [Arg-Phe]4 Octapeptide into Biofunctional Nanoparticles.

ABSTRACT: High-frequency ultrasound treatment is found to be a one-pot green technique to produce peptide-based nanostructures by ultrasound assisted self-assembly of oligopeptides. [Arg-Phe]4 octapeptides, consisting of alternating arginine (Arg/R) and phenylalanine (Phe/F) sequences, were subjected to 430 kHz ultrasound in aqueous solution in the absence of any external agents, to form [RF]4 nanoparticles ([RF]4-NPs), ~220 nm in diameter. A comprehensive analysis of the obtained nanoparticles demonstrated that the aromatic moieties of the oligopeptides can undergo oxidative coupling to form multiple oligomeric species, which then self-assemble into well-defined fluorescent nanoparticles. [RF]4-NPs were functionalized with polyethylene glycol (PEGylated) to improve their colloidal stability. Unlike the parent peptide, the PEGylated [RF]4-NPs showed limited cytotoxicity towards MDA-MB-231 cells. Furthermore, the intracellular trafficking of PEGylated [RF]4-NPs was investigated after incubation with MDA-MB-231 cells to demonstrate their efficient endo-lysosomal escape. This work highlights that the combined use of ultrasonic technologies and peptides enables easy fabrication of nanoparticles, with potential application in drug delivery.

SUBMITTER: Baral A

PROVIDER: S-EPMC7558974 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sono-Assembly of the [Arg-Phe]4 Octapeptide into Biofunctional Nanoparticles.

Baral Anshul A Bhangu Sukhvir K SK Cimino Rita R Pelin Juliane N B D JNBD Alves Wendel A WA Chattopadhyay Santanu S Ashokkumar Muthupandian M Cavalieri Francesca F

Nanomaterials (Basel, Switzerland) 20200908 9

High-frequency ultrasound treatment is found to be a one-pot green technique to produce peptide-based nanostructures by ultrasound assisted self-assembly of oligopeptides. [Arg-Phe]4 octapeptides, consisting of alternating arginine (Arg/R) and phenylalanine (Phe/F) sequences, were subjected to 430 kHz ultrasound in aqueous solution in the absence of any external agents, to form [RF]4 nanoparticles ([RF]4-NPs), ~220 nm in diameter. A comprehensive analysis of the ...[more]

PMID: 32911613

Similar Datasets

Project description:Diphenylalanine is an amyloidogenic building block that can form a versatile array of supramolecular materials. Its shortcomings, however, include the uncontrolled hierarchical assembly into microtubes of heterogeneous size distribution and well-known cytotoxicity. This study rationalized heterochirality as a successful strategy to address both of these pitfalls and it provided an unprotected heterochiral dipeptide that self-organized into a homogeneous and optically clear hydrogel with excellent ability to sustain fibroblast cell proliferation and viability. Substitution of one l-amino acid with its d-enantiomer preserved the ability of the dipeptide to self-organize into nanotubes, as shown by single-crystal XRD analysis, whereby the pattern of electrostatic and hydrogen bonding interactions of the backbone was unaltered. The effect of heterochirality was manifested in subtle changes in the positioning of the aromatic side chains, which resulted in weaker intermolecular interactions between nanotubes. As a result, d-Phe-l-Phe self-organized into homogeneous nanofibrils with a diameter of 4 nm, corresponding to two layers of peptides around a water channel, and yielded a transparent hydrogel. In contrast with homochiral Phe-Phe stereoisomer, it formed stable hydrogels thermoreversibly. d-Phe-l-Phe displayed no amyloid toxicity in cell cultures with fibroblast cells proliferating in high numbers and viability on this biomaterial, marking it as a preferred substrate over tissue-culture plastic. Halogenation also enabled the tailoring of d-Phe-l-Phe self-organization. Fluorination allowed analogous supramolecular packing as confirmed by XRD, thus nanotube formation, and gave intermediate levels of bundling. In contrast, iodination was the most effective strategy to augment the stability of the resulting hydrogel, although at the expense of optical transparency and biocompatibility. Interestingly, iodine presence hindered the supramolecular packing into nanotubes, resulting instead into amphipathic layers of stacked peptides without the occurrence of halogen bonding. By unravelling fine details to control these materials at the meso- and macro-scale, this study significantly advanced our understanding of these systems.

Project description:The tremendous social and economic impact of thrombotic disorders, together with the considerable risks associated to the currently available therapies, prompt for the development of more efficient and safer anticoagulants. Novel peptide-based thrombin inhibitors were identified using in silico structure-based design and further validated in vitro. The best candidate compounds contained both L- and D-amino acids, with the general sequence D-Phe(P3)-Pro(P2)-D-Arg(P1)-P1'-CONH₂. The P1' position was scanned with L- and D-isomers of natural or unnatural amino acids, covering the major chemical classes. The most potent non-covalent and proteolysis-resistant inhibitors contain small hydrophobic or polar amino acids (Gly, Ala, Ser, Cys, Thr) at the P1' position. The lead tetrapeptide, D-Phe-Pro-D-Arg-D-Thr-CONH₂, competitively inhibits α-thrombin's cleavage of the S2238 chromogenic substrate with a K(i) of 0.92 µM. In order to understand the molecular details of their inhibitory action, the three-dimensional structure of three peptides (with P1' L-isoleucine (fPrI), L-cysteine (fPrC) or D-threonine (fPrt)) in complex with human α-thrombin were determined by X-ray crystallography. All the inhibitors bind in a substrate-like orientation to the active site of the enzyme. The contacts established between the D-Arg residue in position P1 and thrombin are similar to those observed for the L-isomer in other substrates and inhibitors. However, fPrC and fPrt disrupt the active site His57-Ser195 hydrogen bond, while the combination of a P1 D-Arg and a bulkier P1' residue in fPrI induce an unfavorable geometry for the nucleophilic attack of the scissile bond by the catalytic serine. The experimental models explain the observed relative potency of the inhibitors, as well as their stability to proteolysis. Moreover, the newly identified direct thrombin inhibitors provide a novel pharmacophore platform for developing antithrombotic agents by exploring the conformational constrains imposed by the D-stereochemistry of the residues at positions P1 and P1'.

Dataset Information

Sono-Assembly of the [Arg-Phe]4 Octapeptide into Biofunctional Nanoparticles.

Publications

Sono-Assembly of the [Arg-Phe]<sub>4</sub> Octapeptide into Biofunctional Nanoparticles.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets