Aromatic Dipeptides Research Articles

Accelerated charge transfer in water-layered peptide assemblies.

Bioinspired assemblies bear massive potential for energy generation and storage. Yet, biological molecules have severe limitations for charge transfer. Here, we report l-tryptophan-d-tryptophan assembling architectures comprising alternating water and peptide layers. The extensive connection of water molecules results in significant dipole-dipole interactions and piezoelectric response that can be further engineered by doping via iodine adsorption or isotope replacement with no change in the chemical composition. This simple system and the new doping strategies supply alternative solutions for enhancing charge transfer in bioinspired supramolecular architectures.

Tubular to spherical mesoscopic self‐assembly of C‐ and N‐termini capped dileucines

AbstractAmong the plethora of aromatic and aliphatic dipeptide sequences that are successfully employed in nanoarchitecture and nanotechnology, dileucines (Leu‐Leu) is known for its self‐sorting behavior like diphenylalanine (Phe‐Phe), the most explored motif till date. However, only a few reports demonstrate the effects of capping groups on Leu‐Leu self‐assembly. Hence, to understand the effect of hydrophobic substituent on C‐/N‐termini, a series of Leu‐Leu derivatives are prepared and their self‐assembled morphology is evaluated. Spherical and tubular mesoscopic morphologies of C‐ and N‐termini capped Leu‐Leu owing to H‐bonding, π‐π stacking and van der Waals interactions are reported. Attachment of alkynes (propyne) at C‐termini results in micro‐tubes and rods for Boc‐Leu‐Leu‐Propyne and Fc‐Leu‐Leu‐Propyne, respectively. Hollow morphology was observed and substantiated by TEM and confocal microscopy. These micro‐tubes and micro‐rods transform into spherical nanoparticles after click conjugation at C‐termini which clearly show the effect of chemical modification on their self‐assembly. Therefore, subtle variations of capping groups result in remarkable changes of self‐assembled morphology, which suggests that the terminal capping is an important factor for rational design of short peptide‐based biomaterial.

Stable and optoelectronic dipeptide assemblies for power harvesting.

Low biocompatibility or engineerability of conventional inorganic materials limits their extensive application for power harvesting in biological systems or at bio-machine interfaces. In contrast, intrinsically biocompatible peptide self-assemblies have shown promising potential as a new type of ideal components for eco-friendly optoelectronic energy-harvesting devices. However, the structural instability, weak mechanical strength, and inefficient optical or electrical properties severely impede their extensive application. Here, we demonstrate tryptophan-based aromatic dipeptide supramolecular structures to be direct wide-gap semiconductors. The molecular packings can be effectively modulated by changing the peptide sequence. The extensive and directional hydrogen bonding and aromatic interactions endow the structures with unique rigidity and thermal stability, as well as a wide-spectrum photoluminescence covering nearly the entire visible region, optical waveguiding, temperature/irradiation-dependent conductivity, and the ability to sustain quite high external electric fields. Furthermore, the assemblies display high piezoelectric properties, with a measured open-circuit voltage of up to 1.4 V. Our work provides insights into using aromatic short peptide self-assemblies for the fabrication of biocompatible, miniaturized electronics for power generation with tailored semiconducting optoelectronic properties and improved structural stability.

Formation, Identification, and Occurrence of New Bromo- and Mixed Halo-Tyrosyl Dipeptides in Chloraminated Water.

Dipeptides are widely present in surface water and serve as precursors to form disinfection byproducts (DBPs) during disinfection (e.g., chloramination). Bromide (Br-) and iodide (I-) are common in many source waters, enhancing Br- and I-DBP formation. Recently Cl-, I-, and Cl-I-dipeptides were identified after chloramination of tyrosyl dipeptides in the presence of I- and were detected in authentic disinfected drinking water samples. However, the formation and occurrence of Br- and mixed halogen (Cl, Br, and/or I)-dipeptides in disinfected water have not been studied. Here we investigated the formation of halogenated dipeptides from three aromatic dipeptides, phenylalanylglycine (Phe-Gly), tyrosylalanine (Tyr-Ala), and tyrosylglycine (Tyr-Gly), under chloramination in the presence of Br- and I- at environmentally relevant levels ([Br-] and [I-], 0 and 0 μg L-1, 6 and 30 μg L-1, 30 and 30 μg L-1, 150 and 30 μg L-1, 300 and 30 μg L-1, and 900 and 30 μg L-1, respectively). For the first time, N-Br- and N,N-di-Br- as well as N-Br- N-Cl- and N-Br-3-I-tyrosyl dipeptides were identified using infusion electrospray quadrupole time-of-flight mass spectrometry. Tyrosyl dipeptides produced N-Cl-, 3-I-/3,5-di-I-, and N-Cl-3-I-tyrosyl dipeptides, while Phe-Gly formed only N-Cl-/ N, N-di-Cl-Phe-Gly. To determine halogenated dipeptides in authentic water samples, we developed a new method of solid phase extraction and high-performance liquid chromatography with quadrupole ion trap mass spectrometry using reaction monitoring. 3,5-Di-I-Tyr-Ala and N-Br-Tyr-Ala were detected in treated water but not in the corresponding raw water, warranting further investigation into the occurrence of halogenated peptides in other drinking water systems.

Probing the Nature of Noncovalent Interactions in Dimers of Linear Tyrosine-Based Dipeptides.

Tyrosine-based dipeptides self-assemble to form higher order structures. To gain insights into the nature of intermolecular interactions contributing to the early stages of the self-assembly of aromatic dipeptides, we study the dimers of linear dityrosine (YY) and tryptophan–tyrosine (WY) using quantum-chemical methods with dispersion corrections and universal solvation model based on density in combination with energy decomposition and natural bond orbital (NBO) analyses. We find that hydrogen bonding is a dominant stabilizing force. The lowest energy structure for the linear YY dimer is characterized by Ocarboxyl···H(O)tyr. In contrast, the lowest energy dimer of linear WY is stabilized by Ocarboxyl···H(N)trp and πtyr···πtyr. The solvent plays a critical role as it can change the strength and nature of interactions. The lowest energy for linear WY dimer in acetone is stabilized by Ocarboxyl···H(O)tyr, πtrp···H(C), and πtrp···H(N). The ΔG of dimerization and stabilization energies of solvated dipeptides reveal that the dipeptide systems are more stable in the solvent phase than in gas phase. NBO confirms increased magnitudes for donor–acceptor interaction for the solvated dipeptides.

Tyrosine-Rich Peptides as a Platform for Assembly and Material Synthesis.

The self‐assembly of biomolecules can provide a new approach for the design of functional systems with a diverse range of hierarchical nanoarchitectures and atomically defined structures. In this regard, peptides, particularly short peptides, are attractive building blocks because of their ease of establishing structure–property relationships, their productive synthesis, and the possibility of their hybridization with other motifs. Several assembling peptides, such as ionic‐complementary peptides, cyclic peptides, peptide amphiphiles, the Fmoc‐peptide, and aromatic dipeptides, are widely studied. Recently, studies on material synthesis and the application of tyrosine‐rich short peptide‐based systems have demonstrated that tyrosine units serve as not only excellent assembly motifs but also multifunctional templates. Tyrosine has a phenolic functional group that contributes to π–π interactions for conformation control and efficient charge transport by proton‐coupled electron‐transfer reactions in natural systems. Here, the critical roles of the tyrosine motif with respect to its electrochemical, chemical, and structural properties are discussed and recent discoveries and advances made in tyrosine‐rich short peptide systems from self‐assembled structures to peptide/inorganic hybrid materials are highlighted. A brief account of the opportunities in design optimization and the applications of tyrosine peptide‐based biomimetic materials is included.

Ferroferric Oxide Significantly Affected Production of Soluble Microbial Products and Extracellular Polymeric Substances in Anaerobic Methanogenesis Reactors.

Conductive materials facilitate direct interspecies electron transfer between acidogens and methanogens during methane (CH4) production. Soluble microbial products (SMP) and extracellular polymeric substances (EPS) produced by microorganisms might act as the electron shuttle between microorganisms and conductive materials. In this study, effects of conductive ferroferric oxide (Fe3O4) on anaerobic treatment process and the production of SMP and EPS were investigated. The maximum CH4 production rate was enhanced by 23.3% with the dosage of Fe3O4. The concentrations of proteins, polysaccharides, and humic substances in tightly bound EPS (T-EPS) were promoted, suggesting that extracellular metabolisms were induced by conductive materials. Distribution of potential electron shuttles such as quinone-like substances, flavins, aromatic amino acids, and dipeptides in SMP and EPS phases were comprehensively investigated and these electron shuttles were significantly affected by Fe3O4. Dipeptides consisting of phenylalanine were widely detected in T-EPS of the Fe3O4 reactor, indicating a potential different extracellular electron exchange pattern with the addition of conductive materials.

Optical Sensing of Aromatic Amino Acids and Dipeptides by a Crown-Ether-Functionalized Perylene Bisimide Fluorophore.

The host-guest binding properties of a fluorescent perylene bisimide (PBI) receptor equipped with crown ether were studied in detail with a series of aromatic amino acids and dipeptides by UV/Vis, fluorescence and NMR spectroscopy. Fluorescence titration experiments showed that electron-rich aromatic amino acids and dipeptides strongly quench the fluorescence of the electron-poor PBI host molecule. Benesi-Hildebrand plots of fluorescence titration data confirmed the formation of host-guest complexes with 1:2 stoichiometry. Binding constants determined by global analysis of UV/Vis and fluorescence titration experiments revealed values between 103 m-1 and 105 m-1 in acetonitrile/methanol (9:1) at 23 °C. These data showed that amino acid l-Trp having an indole group and dipeptides containing this amino acid bind to the PBI receptor more strongly than other amino acids and dipeptides investigated here. For dipeptides containing l-Trp or l-Tyr, the binding strength is dependent on the distance between the ammonium group and the aromatic unit of the amino acids and dipeptides leading to a strong sensitivity for Ala-Trp dipeptide. 1D and 2D NMR experiments also corroborated 1:2 host-guest complexation and indicated formation of two diastereomeric species of host-guest complexes. The studies have shown that a properly functionalized PBI fluorophore functions as a molecular probe for the optical sensing of aromatic amino acids and dipeptides.

Conformational structures and vibrational spectroscopic investigation of isolated dityrosine and tryptophan-tyrosine dipeptides: A theoretical study

Aromatic peptides can form dipeptides which could then self-assemble into nanostructures. However, there is still a lack of fundamental understanding between structures and properties of these materials. We use dispersion-corrected density functional theory and second-order Møller Plesset perturbation theory to study a few lowest energy structures and the corresponding vibrational spectra of linear and cyclic dityrosine (YY) and tryptophan-tyrosine (WY), the building blocks of four different aromatic dipeptide nanotubes. The variation in relative energies predicted by the different methods indicates that a judicious choice of levels of theory is critical for these systems. We find common geometrical features for the systems of interest. For linear YY and WY, the most stable conformers are characterized by intermolecular hydrogen bonding of the carboxylic hydroxyl group with the carbonyl of the amide. For cyclic YY and WY, the most stable conformers assume a slightly puckered boat structure for the diketopiperazine ring with the aromatic side chains in pseudoaxial and pseudoequatorial positions. All the systems considered in this study possess at least two aromatic groups suggesting that π-π stacking interaction, in addition to hydrogen bonding, is an essential factor behind aggregation of self-assembled structures from peptide-based molecular frameworks.

Crystalline Dipeptide Nanobelts Based on Solid-Solid Phase Transformation Self-Assembly and Their Polarization Imaging of Cells.

Controlled phase transformation involving biomolecular organization to generate dynamic biomimetic self-assembly systems and functional materials is currently an appealing topic of research on molecular materials. Herein, we achieve by ultrasonic irradiation the direct solid-solid transition of bioinspired dipeptide organization from triclinic structured aggregates to nanofibers and eventually to monoclinic nanobelts with strong polarized luminescence. It is suggested that the locally high temperature and pressure produced by cavitation effects cleaves the hydrophobic, π-π stacking or self-locked intramolecular interactions involved in one phase state and then rearranges the molecular packing to form another well-ordered aromatic dipeptide crystalline structure. Such a sonication-modulated solid-solid phase transition evolution is governed by distinct molecular interactions at different stages of structural organization. The resulting crystalline nanobelts are for the first time applied for polarization imaging of cells, which can be advantageous to directly inspect the uptake and fate of nanoscale delivery platforms without labeling of fluorescent dyes. This finding provides a new perspective to comprehend the dynamic evolution of biomolecular self-organization with energy supply by an external field and open up a facile and versatile approach of using anisotropic nanostructures for polarization imaging of cells and even live organisms in future.

Aromatic dipeptide Trp–Ala can be transported by Arabidopsis peptide transporters AtPTR1 and AtPTR5

ABSTRACTDipeptides with an aromatic residue at the N–terminal position induced lower inward currents or blocked leak currents in Xenopus oocytes expressing the proton-coupled peptide transporter AtPTR1 or AtPTR5 of Arabidopsis thaliana compared with dipeptides with an aromatic residue at the C–terminal position. Here, AtPTR1 and AtPTR5 were expressed in a yeast mutant of peptide transporter (ptr2) with tryptophan auxotrophy. Growth assays showed that Trp–Ala could be transported by both AtPTR1 and AtPTR5 as efficiently as Ala–Trp. Our data suggested that the previous finding in Xenopus oocytes might be an artifact of heterologous expression, and that AtPTR1 and AtPTR5 expressed in yeast could transport dipeptides with an aromatic residue at the N–terminal position.

ChemInform Abstract: Peptide Self‐Assembly: Thermodynamics and Kinetics

AbstractReview: 169 refs.

Publisher's Note: "Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study" [J. Chem. Phys. 144, 245103 (2016)

Publisher's Note: "Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study" [J. Chem. Phys. 144, 245103 (2016)

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study.

The time-resolved parallel artificial membrane permeability assay with fluorescence detection and comprehensive computer simulations are used to study the passive permeation of three aromatic dipeptides-N-acetyl-phenylalanineamide (NAFA), N-acetyltyrosineamide (NAYA), and N-acetyl-tryptophanamide (NATA) through a 1,2-dioleoyl-sn-glycero-3-phospocholine (DOPC) lipid bilayer. Measured permeation times and permeability coefficients show fastest translocation for NAFA, slowest for NAYA, and intermediate for NATA under physiological temperature and pH. Computationally, we perform umbrella sampling simulations to model the structure, dynamics, and interactions of the peptides as a function of z, the distance from lipid bilayer. The calculated profiles of the potential of mean force show two strong effects-preferential binding of each of the three peptides to the lipid interface and large free energy barriers in the membrane center. We use several approaches to calculate the position-dependent translational diffusion coefficients D(z), including one based on numerical solution the Smoluchowski equation. Surprisingly, computed D(z) values change very little with reaction coordinate and are also quite similar for the three peptides studied. In contrast, calculated values of sidechain rotational correlation times τrot(z) show extremely large changes with peptide membrane insertion-values become 100 times larger in the headgroup region and 10 times larger at interface and in membrane center, relative to solution. The peptides' conformational freedom becomes systematically more restricted as they enter the membrane, sampling α and β and C7eq basins in solution, α and C7eq at the interface, and C7eq only in the center. Residual waters of solvation remain around the peptides even in the membrane center. Overall, our study provides an improved microscopic understanding of passive peptide permeation through membranes, especially on the sensitivity of rotational diffusion to position relative to the bilayer.

Antifungal membranolytic activity of the tyrocidines against filamentous plant fungi.

The tyrocidines and analogues are cyclic decapeptides produced by Brevibacillus parabrevis with a conserved sequence of cyclo(D-Phe1-Pro2-X3-x4-Asn5-Gln6-X7-Val8-X9-Leu10) with Trp3,4/Phe3,4 in the aromatic dipeptide unit, Lys9/Orn9 as their cationic residue and Tyr (tyrocidines), Trp (tryptocidines) or Phe (phenicidines) in position 7. Previous studies indicated they have a broad antifungal spectrum with the peptides containing a Tyr residue in position 7 being more active than those with a Phe or Trp residue in this position. Detailed analysis of antifungal inhibition parameters revealed that Phe3-D-Phe4 in the aromatic dipeptide unit lead to more consistent activity against the three filamentous fungi in this study. These peptides exhibited high membrane activity and fast leakage kinetics against model membranes emulating fungal membranes, with selectivity towards ergosterol containing membranes. More fluid membranes and doping of liposomes with the sphingolipid, glucosylceramide, led to a decreased permeabilising activity. Peptide-induced uptake of membrane impermeable dyes was observed in hyphae of both Fusarium solani and Botrytis cinerea, with uptake more pronounced at the hyphal growth tips that are known to contain ergosterol-sphigolipid rich lipid rafts. Tyrocidine interaction with these rafts may lead to the previously observed fungal hyperbranching. However, the leakage of model membranes and Bot. cinerea did not correlate directly with the antifungal inhibition parameters, indicating another target or mode of action. Proteinase K treatment of target fungi had a minimal influence or even improved the tyrocidine activity, ruling out a mannoprotein target in the fungal cell wall. β-glucanase treatment of Bot. cinerea did not significantly affect the tyrocidine activity, but there was a significant loss in activity towards the β-glucanase treated F.solani. This study showed the tyrocidine antifungal membrane activity is selective towards ergosterol and possibly lipid rafts, but also point to additional targets such as the cell wall β-glucans that could modulate their activity.

Counterion‐Directed, Structurally Tunable Assembly of Hydrogels, Membranes, and Sacs at Aqueous Liquid–Liquid Interfaces

Counterions play a crucial role in directing the self‐assembly of components in biological systems. In this paper, the self‐assembly of aromatic dipeptides and polysaccharide chitosan is reported at an aqueous liquid–liquid interface. It is shown that subtle modulations in the counterions and pH values allow changes in the self‐assembling pathway localized at the aqueous liquid–liquid interface and thus fabricate materials with distinct structural features and functions, from hydrogels to membranes and hollow sacs. The hydrogel shows strong birefringence and the directional freeze of the gel leads to the formation of macroscopically layered domains with sizes up to centimeters. Moreover, the membranes and sacs exhibit high mechanical strengths, tunable permeabilities, and pH‐responsiveness and have good performance for controlled release. Compared with other self‐assembling peptides, aromatic dipeptides are much smaller and easier to synthesize (low cost). The self‐assembly of these dipeptides with functional polysaccharide chitosan has potential applications in many areas, including large‐scale manufacture of microcapsules for controlled drug release and enzyme immobilization.

Metastable hydrogels from aromatic dipeptides.

We demonstrate that the well-known self-assembling dipeptide diphenylalanine (FF) and its amidated derivative (FF-NH2) can form metastable hydrogels upon sonication of the dipeptide solutions. The hydrogels show instantaneous syneresis upon mechanical contact resulting in rapid expulsion of water and collapse into a semi-solid gel.

Inversion of Supramolecular Chirality by Sonication-Induced Organogelation.

Natural helical structures have inspired the formation of well-ordered peptide-based chiral nanostructures in vitro. These structures have drawn much attention owing to their diverse applications in the area of asymmetric catalysts, chiral photonic materials, and nanoplasmonics. The self-assembly of two enantiomeric fluorinated aromatic dipeptides into ordered chiral fibrillar nanostructures upon sonication is described. These fibrils form organogels. Our results clearly indicate that fluorine-fluorine interactions play an important role in self-assembly. Circular dichroism analysis revealed that both peptides (peptides 1 and 2), containing two fluorines, depicted opposite cotton effects in their monomeric form compared with their aggregated form. This shows that supramolecular chirality inversion took place during the stimuli-responsive self-aggregation process. Conversely, peptide 3, containing one fluorine, did not exhibit chirality inversion in sonication-induced organogelation. Therefore, our results clearly indicate that fluorination plays an important role in the organogelation process of these aromatic dipeptides. Our findings may have broad implications regarding the design of chiral nanostructures for possible applications such as chiroptical switches, asymmetric catalysis, and chiral recognitions.

Ultrasonic nebulization extraction/low pressure photoionization mass spectrometry for direct analysis of chemicals in matrices

A novel ultrasonic nebulization extraction/low-pressure photoionization (UNE-LPPI) system has been designed and employed for the rapid mass spectrometric analysis of chemicals in matrices. An ultrasonic nebulizer was used to extract the chemicals in solid sample and nebulize the solvent in the nebulization cell. Aerosols formed by ultrasonic were evaporated by passing through a transferring tube, and desolvated chemicals were ionized by the emitted light (10.6 eV) from a Krypton discharge lamp at low pressure (∼68 Pa). First, a series of semi/non-volatile compounds with different polarities, such as polycyclic aromatic hydrocarbons (PAHs), amino acids, dipeptides, drugs, nucleic acids, alkaloids, and steroids were used to test the system. Then, the quantification capability of UNE-LPPI was checked with: 1) pure chemicals, such as 9,10-phenanthrenequinone and 1,4-naphthoquinone dissolved in solvent; 2) soil powder spiked with different amounts of phenanthrene and pyrene. For pure chemicals, the correlation coefficient (R2) for the standard curve of 9,10-phenanthrenequinone in the range of 3 ng–20 μg mL−1 was 0.9922, and the measured limits of detection (LOD) was 1 ng ml−1. In the case of soil powder, linear relationships for phenanthrene and pyrene from 10 to 400 ng mg−1 were obtained with correlation coefficients of 0.9889 and 0.9893, respectively. At last, the feasibility of UNE-LPPI for the detection of chemicals in real matrices such as tablets and biological tissues (tea, Citrus aurantium peel and sage (Salvia officinalis) leaf) were successfully demonstrated.

Suzuki–Miyaura Diversification of Amino Acids and Dipeptides in Aqueous Media

AbstractThe Suzuki–Miyaura derivatisation of free amino acids, peptides and proteins is an attractive area with considerable potential utility for medicinal chemistry and chemical biology. Here we report the modification of unprotected and Boc‐protected aromatic amino acids and dipeptides in aqueous media, enabling heteroarylation and vinylation. We systematically investigate the impact of the peptide backbone and adjacent amino acid residues upon the reaction. Our studies reveal that although asparagine and histidine hinder the reaction, by utilising dppf, a ferrocene‐based bidentate phosphine ligand, cross coupling of halophenylalanine or halotryptophan adjacent to such a residue could be enabled. Our studies reveal dppf to have good compatibility with all unprotected, proteinogenic amino acid side chains.