Diphenylalanine Peptide Research Articles

Chirality-Dependent Copper-Diphenylalanine Assemblies with Tough Layered Structure and Enhanced Catalytic Performance.

Chiral regulation to prepare functional materials has aroused considerable interest in recent years. However, little is known on the effect of chirality of ligands in the metal-organic coordination assembly process. We report the self-assembly of diphenylalanine peptide (Phe-Phe, FF), the core fragment of Aβ protein, with metal copper ion (Cu2+) into metal-organic assemblies with chirality-encoded structures and properties. The chirality-dependent metal-dipeptide assembles with different morphologies and supramolecular chirality were obtained by facile changing of the FF chirality. Single-crystal results indicate that (L)-FF coordinated with Cu2+ into a cross-chain structure with a five-coordinated style, while the racemates of (L+D)-FF with Cu2+ crystallized into an (L)-Cu2+-(D)-Cu2+ alternated four-coordinating structure, enabling a higher mechanical and catalytic performance. The Young's modulus of (L+D)-FF-Cu is as high as 34.36 GPa, which is 2.45 times higher than that of (L)-FF-Cu. Furthermore, both of them follow the characteristic enzyme kinetics and show higher catalytic activity than natural laccase at the same mass concentration. Specifically, the calculated catalytic efficiency (kcat/KM) of (L+D)-FF-Cu is 1.14 times higher than that of (L)-FF-Cu, and the (L+D)-FF-Cu shows significantly enhanced stability and reusability compared with (L)-FF-Cu. The results reveal that highly functional materials could be constructed by encoding the chirality of molecular building blocks.

Structural Transition-Induced Raman Enhancement in Bioinspired Diphenylalanine Peptide Nanotubes.

Semiconducting materials are increasingly proposed as alternatives to noble metal nanomaterials to enhance Raman scattering. We demonstrate that bioinspired semiconducting diphenylalanine peptide nanotubes annealed through a reported structural transition can support Raman detection of 10–7 M concentrations for a range of molecules including mononucleotides. The enhancement is attributed to the introduction of electronic states below the conduction band that facilitate charge transfer to the analyte molecule. These results show that organic semiconductor-based materials can serve as platforms for enhanced Raman scattering for chemical sensing. As the sensor is metal-free, the enhancement is achieved without the introduction of electromagnetic surface-enhanced Raman spectroscopy.

Peptide Coassembly to Enhance Piezoelectricity for Energy Harvesting.

The discovery of piezoelectricity in self-assembled peptide nanostructures opens an avenue to a new regime of piezoelectric materials and enables the fundamental investigation of electromechanical coupling in biomaterials. However, strategies for fabricating peptides with desired properties are still lacking. We find that a peptide-based coassembly process effectively controls the properties of peptide nanomaterials and demonstrates their application potential in nanogenerators. The composing peptides and their concentration influence the morphology, molecular property, and physical property of coassembled crystals. Compared with self-assembled diphenylalanine peptides, the coassembled peptides of diphenylalanine and phenylalanine-tryptophan show a 38% increase in piezoelectric coefficient, and the resulting harvesting device shows nearly a 3-fold increase in open-circuit voltage outputs.

Diphenylalanine-based degradable piezoelectric nanogenerators enabled by polylactic acid polymer-assisted transfer

Biocompatible and biodegradable energy harvesters are of significance for biomedical application as an alternative energy source without causing adverse effects to the human body. Intrinsically biocompatible diphenylalanine peptides with good piezoelectric, dielectric, and mechanical properties are promising materials for energy conversion. Herein, we report a degradable piezoelectric nanogenerator (PENG) based on a free-standing polylactic acid film with embedded diphenylalanine microrods arrays. The stiff polylactic acid polymer can remove stiff microrods from rigid silicon substrate and transfer uniformly external forces to them for energy conversion. The PENG produces a maximal output voltage of 1.78 V and a power density of 1.56 W m−3. Furthermore, the device exhibits full dissolution in alkaline solution, acidic solution and phosphate-buffered saline solution after 25 days at 60 ℃. The degradable PENG provides a viable solution to power transient electronics and reduce the environmental footprint of devices.

A green fluorescent protein chromophore analogue to promote self-assembly of diphenylalanine into fluorescent microtubes

It is known that misfolding and aggregation of amyloid-beta (Aβ) peptide was thought to be the causing of Alzheimer's disease (AD). Until now, there are no effective drugs for this disease. Therefore, it is necessary to develop excellent probes for early diagnosis and assisting drug research and development of AD. Diphenylalanine peptide (FF), as a key and the smallest core recognition sequence of amyloid-beta (Aβ) peptide, has attracted much attention. In this paper, we designed and synthesized meta- and para-amino green fluorescent protein chromophore analogues m-DBI and p-DBI. Comparing their fluorescence properties, we found that m-DBI displayed relatively strong fluorescence in aprotic organic solvents due to a large barrier for the Z→E photoisomerization, while it showed weak fluorescence in protic solvents as a result of solvent-solute H-bonding interactions. Importantly, it could drive and assemble with FF into microtubes with “turn-on” fluorescence. In contrast, p-DBI exhibited very weak fluorescence in both protic and aprotic solvents, which is due to the ultrafast Z→E photoisomerization. Furthermore, it could not co-assemble with FF and even displayed weak fluorescence in solid state. In addition, FF-m-DBI co-assembly microtubes could be partially disassembled through incubating with a potent inhibitor of Aβ aggregation EGCG, accompanied by a decrease in fluorescence intensity, shows the potential application of screening possible inhibitor molecules of AD diseases.

Aggregation-enhanced emission of metal nanoclusters triggered by peptide self-assembly and application in chymotrypsin inhibitor screening

Herein, a new strategy is developed to induce the aggregation of glutathione-capped gold nanoclusters (GSH-AuNCs) by self-assembly of peptide. The diphenylalanine peptide (L-Phe-l-Phe, FF) self-assembles in aqueous solution into the nano-net structure (FF-Nanonet, FFN). With self-assembly of FF, GSH-AuNCs aggregate in the network of FFN to form a dual-emission probe, called FF-N@GSH-AuNCs. One emission is from the self-assembled FFN at 470 nm, and the other one is the aggregation-induced enhanced emission (AIEE) of the GSH-AuNCs at 575 nm. Due to the hydrolysis of FF by chymotrypsin (CHT), the peptide bond on the carboxyl side of the phenylalanine is cleaved and the AIEE from GSH-AuNCs becomes faint because the released nanoclusters are dispersed in the solution again. Therefore, FF-N@GSH-AuNCs can be applied to screen and evaluate the CHT inhibitors. The inhibitory effects of four ingredients from natural products (i.e. epigallocatechin gallate (EGCG), tannic acid, oleanolic acid, and ursolic acid) on CHT activity have been studied. Oleanolic acid and ursolic acid are invalid. The half maximal inhibitory concentration (IC 50) values of EGCG and tannic acid are 13.9 and 19.2 μM, respectively. The screening results show that these two compounds have significant inhibitory effects on CHT.

Three-Dimensional Printing of Self-Assembled Dipeptides.

Peptide-based materials are emerging as smart building blocks for nanobiodevices due to the programmability of their properties via the molecular constituents or arrangements. Many clever molecular self-assembly approaches have been devised to produce peptide crystalline structures. However, their freeform shaping remains a challenge due to the intrinsic self-assembly nature. Here, we report the fabrication of freeform, crystalline diphenylalanine (FF) peptide structures by combining meniscus-guided 3D printing with molecular self-assembly. Self-assembly in 3D-printed FF arises from mild thermal activation under precise temperature control of the build platform. After thorough characterizations, we demonstrate layer-by-layer, crystalline 3D printing with a high spatial resolution of 2 μm laterally and 200 nm vertically. The 3D-printed FF exhibits piezoelectricity originating from its crystalline character, showing the potential to become a key constituent for bioelectronic devices. We expect this technique to open up the possibility to create functional devices based on self-assembled organic materials without design restrictions.

Preparation of self-assembling Litsea cubeba essential oil/ diphenylalanine peptide micro/nanotubes with enhanced antibacterial properties against Staphylococcus aureus biofilm

The contamination of foodborne pathogens biofilms presents a serious challenge for global food safety, attributed to their rapid diffusion and high antimicrobial resistance. Herein, we demonstrated that Litsea cubeba essential oil (LC-EO) has sufficient antibacterial activity to eradicate S. aureus biofilm. After 4 h treatment of 2 mg/mL LC-EO, the bacterial density inside the biofilm decreased 75.89%. The study on antibiofilm mechanism indicated that during LC-EO treatment, the adhesion of S. aureus was weakened, and the transcription level of ica operon genes (biofilm formation-related) suffered varying degrees of inhibition. In addition, for improving the stability and antibiofilm activity of LC-EO, a LC-EO-loaded peptide micro/nanotubes structure (LC-EO/FNTs) was further prepared in this study via combination with diphenylalanine self-assembly technology. Compared with LC-EO treatment alone, the prepared LC-EO/FNTs showed better eradication effect on S. aureus biofilm with enhanced penetrability across the dense extracellular polymers matrix. Finally, a stable antibacterial effect of LC-EO/FNTs was also obtained with application on different handmade soybean products. This study provides evidence of an innovative strategy for antibiofilm applications of natural antibacterial agents and materials in food matrix.

Modeling and physical properties of diphenylalanine peptide nanotubes containing water molecules

DFT (VASP) and semi-empirical (HyperChem) calculations for the D-chiral diphenylalanine (D-FF) peptide nanotube (PNT) structures, empty and filled with water/ice clusters, are presented and analyzed. The obtained results show that after the optimization the dipole moment and polarization of both D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquires a helix-like structure similar to that of D-FF PNT. Possible ferroelectric properties of the tubular water/ice helix-like cluster inside the D-FF PNT are discussed.

Spin coating mediated morphology modulation in self assembly of peptides.

Controlling the morphology and nanostructure of self-assembled peptide molecules is of fundamental importance to chemistry and material science due to their bioactivity in both in vivo and in vitro settings, ability to act as templates for conjugating bio-recognition elements, hybrid supramolecular assembly, possible detection and treatment of diseases and so on. In this article, we show that spin coating, a widely utilized method for obtaining ultra-thin polymer films, has been utilised to modulate the self-assembly of peptide molecules, which has traditionally been achieved by chemical functionalisation of the molecules. With the specific example of diphenylalanine-based peptide molecules, we show that a variety of self-assembled architectures such as long fibrils, short fibrils, globules, nanodots, and so on, spanning over large areas can be obtained by simultaneously varying the spinning speed (RPM) and the solution concentration (Cp) during spin coating. We correlate the variation in morphology to a transition from spin dewetting at very low Cp (or high RPM) to the formation of continuous films at high Cp (or low RPM) during the initial stage of spin coating. We further show the generality of the approach by achieving distinct self-assembled morphologies with diphenylalanine analogues with different C-terminal and N-terminal groups by modulation of spin coating parameters, though the exact morphology obtained under identical coating conditions depends on the chemical nature of the peptide molecules. The work opens up a new possible route for creating complex peptide assemblies on demand by simultaneous control of molecular functionalisation and spin coating parameters vis - a - vis the applied centrifugal force.

Understanding the unusual stiffness of hydrophobic dipeptide crystals.

The hydrophobic diphenylalanine peptide crystal is known to be unusually stiff, with an experimental Young's modulus in the range of 19-27 GPa. Here it is shown by means of density functional theory calculations that phenylalanine-leucine, leucine-phenylalanine, alanine-valine, valine-alanine and valine-valine hydrophobic dipeptide crystals are also unusually stiff, with Young's moduli in the range of 19.7-33.3 GPa. To further our understanding of the origin of that unusual stiffness, a linear correlation is established between Young's modulus and the strength and orientation of the hydrogen bond network developed along the crystals, showing that stiffness in these materials is primarily dictated by hydrogen bonding.

Revisiting the Self-Assembly of Highly Aromatic Phenylalanine Homopeptides.

Diphenylalanine peptide (FF), which self-assembles into rigid tubular nanostructures, is a very short core recognition motif in Alzheimer’s disease β-amyloid (Aβ) polypeptide. Moreover, the ability of the phenylalanine (F or Phe)-homopeptides to self-assemble into ordered nanostructures has been proved. Within this context it was shown that the assembly preferences of this family of compounds is altered by capping both the N- and C-termini using highly aromatic fluorenyl groups (i.e., fluorenyl-9-methoxycarbonyl and 9-fluorenylmethyl ester, named Fmoc and OFm, respectively). In this article the work performed in the field of the effect of the structure and incubation conditions on the morphology and polymorphism of short (from two to four amino acid residues) Phe-homopeptides is reviewed and accompanied by introducing some new results for completing the comparison. Special attention has been paid to the influence of solvent: co-solvent mixture used to solubilize the peptide, the peptide concentration and, in some cases, the temperature. More specifically, uncapped (FF, FFF, and FFFF), N-capped with Fmoc (Fmoc-FF, Fmoc-FFF, and Fmoc-FFFF), C-capped with OFm (FF-OFm), and doubly capped (Fmoc-FF-OFm, Fmoc-FFF-OFm, and Fmoc-FFFF-OFm) Phe-homopeptides have been re-measured. Although many of the experienced assembly conditions have been only revisited as they were previously reported, other experimental conditions have been examined by the first time in this work. In any case, pooling the effect of highly aromatic blocking groups in a single study, using a wide variety of experimental conditions, allows a perspective of how the disappearance of head-to-tail electrostatic interactions and the gradual increase in the amount of π–π stacking interactions, affects the morphology of the assemblies. Future technological applications of Phe-homopeptides can be envisaged by choosing the most appropriate self-assemble structure, defining not only the length of the peptide but also the amount and the position of fluorenyl capping groups.

Self-Assembly of Amyloid-Beta and Its Piezoelectric Properties

Investigating amyloid nanofibril self-assembly, with an emphasis on the electromechanical property of amyloid peptides, namely, piezoelectricity, may have several important implications: 1) the self-assembly process can hinder the biological stability and give rise to the formation of amyloid structures associated with neurodegenerative diseases; 2) investigations in this field may lead to an improved understanding of high-performance, functional biological nanomaterials, 3) new technologies could be established based on peptide self-assembly and the resultant functional properties, e.g., in the creation of a piezoelectric device formed with vertical diphenylalanine peptide tubes as a piezoelectric biosensor, and 4) new knowledge can be generated about neurodegenerative disorders, potentially yielding new therapies. Therefore, in this review, we will present the current investigations associated with self-assembly of amyloid-beta, the mechanisms that generate new structures, as well as theoretical calculations exploring the functionality of the structures under physiological pressure and electric field.

Molecular modeling and computational study of the chiral-dependent structures and properties of the self-assembling diphenylalanine peptide nanotubes, containing water molecules.

DFT (VASP) and semi-empirical (HyperChem) calculations for the L- and D-chiral diphenylalanine (L-FF and D-FF) nanotube (PNT) structures, empty and filled with water/ice clusters, are presented and analyzed. The results obtained show that after optimization, the dipole moment and polarization of both chiral type L-FF and D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquire the helix-like structure similar as L-FF and D-FF PNT. Ferroelectric properties of tubular water/ice helix-like-cluster obtained after optimization inside L-FF and D-FF PNT and total L-FF and D-FF PNT with embedded water/ice cluster are discussed.

Structures and Properties of the Self-Assembling Diphenylalanine Peptide Nanotubes Containing Water Molecules: Modeling and Data Analysis.

The structures and properties of the diphenylalanine (FF) peptide nanotubes (PNTs), both L-chiral and D-chiral (L-FF and D-FF) and empty and filled with water/ice clusters, are presented and analyzed. DFT (VASP) and semi-empirical calculations (HyperChem) to study these structural and physical properties of PNTs (including ferroelectric) were used. The results obtained show that after optimization the dipole moment and polarization of both chiral type L-FF and D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquire the helix-like structure similar as L-FF and D-FF PNT. Ferroelectric properties of tubular water/ice helix-like cluster, obtained after optimization inside L-FF and D-FF PNT, as well of the total L-FF and D-FF PNT with embedded water/ice cluster, are discussed.

Small Molecular Prodrug Amphiphile Self-Assembled AIE Dots for Cancer Theranostics.

A simple and facile one-step method was developed to construct a small molecular prodrug amphiphile self-assembled organic dots CPPG with aggregation-induced emission (AIE) characteristics. Diphenylalanine peptide (FF), which is the essential moiety of the self-assembling peptide-drug conjugate and as its core recognition motifs for molecular self-assembly. In addition, the D-glucose transported protein (GLUT), which is one of the important nutrient transporters and is overexpressed in cancer cells. The conjugation of glycosyl further endues the nanoparticle with good biocompatibility and tumor-targeting ability. Taking advantages of both the cancer cell-targeting capability of small molecular prodrug amphiphile CPPG and the AIE aggregates with strong emission, the prepared CPPG AIE dots can target cancer cells specifically and inhibit the proliferation of cancer cells with good biocompatibility and photostability. Based on the general approach, types of universal organic fluorescent nanoprobes could be facilely constructed for imaging applications and biological therapeutics, which possess the properties of specific recognition and high brightness.

Energy harvesting with peptide nanotube–graphene oxide flexible substrates prepared with electric field and wettability assisted self-assembly

Piezoelectric diphenylalanine peptide nanotubes (PNTs) have recently been demonstrated in energy harvesting applications, typically based on vertically aligned PNTs that generate charge when pressed. In this work, we use a wettability difference and an applied electric field to align PNTs and PNT-based composites on flexible substrates. Open-circuit voltages and short-circuit currents exceeding 6 V and 60 nA, respectively, are achieved by bending the substrate, opening up the use of horizontally aligned PNTs as flexible energy harvesting substrates.

Fmoc-diphenylalanine-based hydrogels as a potential carrier for drug delivery

Abstract Self-assembled hydrogels from 9-fluorenylmethoxycarbonyl-modified diphenylalanine (Fmoc-FF) peptides were evaluated as potential vehicles for drug delivery. During self-assembly of Fmoc-FF, high concentrations of indomethacin (IDM) drugs were shown to be incorporated into the hydrogels. The β-sheet arrangement of peptides was found to be predominant in Fmoc-FF–IDM hydrogels regardless of the IDM content. The release mechanism for IDM displayed a biphasic profile comprising an initial hydrogel erosion-dominated stage followed by the diffusion-controlled stage. Small amounts of polyamidoamine dendrimer (PAMAM) added to the hydrogel (Fmoc-FF 0.5%–IDM 0.5%–PAMAM 0.03%) resulted in a more prolonged IDM release compared with Fmoc-FF 0.5%–IDM 0.5% hydrogel. Furthermore, these IDM-loaded hydrogels demonstrated excellent thixotropic response and injectability, which make them suitable candidates for use as injectable self-healing matrices for drug delivery.

Diphenylalanin nanofibers-inspired synthesis of fluorescent gold nanoclusters for screening of anti-amyloid drugs

Protein misfolding and aggregation into amyloid structures is linked with a number of pathophysiological disorders. In the past decade, significant progresses have been made in the drug discovery strategies against toxic aggregates. Although lack of specificity and high sensitivity for in vitro screening system still seen. Here we demonstrate a new targeting probe based on FF diphenylalanine peptide -protected gold nanoclusters (FF AuNCs). Diphenylalanine peptide has previously been shown to self-assemble into well-ordered fiber like the fibers that are observed in amyloid aggregates. We used of the self-assembly properties along with the ability of FF dipeptide in reduction of gold ions for synthesis of novel Au nanoclusters. We used FF AuNCs for monitoring of effectiveness of anti-amyloid drugs. Fluorescence was considerably diminished when drugs at different concentrations added, due to destruction of the amyloid fibers. Furthermore, the analysis of several components demonstrates significant selectivity against the amyloid disrupting molecules. Prepared FF AuNCs will gain possible strategy for in vitro screening of amyloid disrupting molecules.

Synthesis of antibacterial flower‐like silver nanostructures by self‐assembly of diphenylalanine peptide on graphite

Preparation of silver nanoflowers (Ag NFs) was carried out through the self-assembly process of diphenylalanine (FF) peptide on the graphite surface. Pencil graphite rods were used as a substrate for the self-assembly process. A reduction reaction by hydrazine was employed in the synthesis procedure of the Ag NFs. scanning electron microscope, Fourier transform infrared spectroscopy (FT-IR) spectroscopy and X-ray diffraction (XRD) were employed to characterise the obtained Ag NFs. The morphological analysis of the Ag NFs revealed assemblies constructed by multiple sheet nanostructures designed as flower petals and positioned in the form of 3D semi-spherical arrangements. The successful synthesis of Ag NFs was confirmed by FT-IR characteristic bands of FF and Ag components. The cubic lattice structure of the Ag NFs was revealed by XRD. Standard Kirby–Bauer disk diffusion tests using Gram-positive and Gram-negative bacterial strains exhibited the promising antibacterial performance of the Ag NFs against all of the tested bacterial species.