Dipeptide Molecules Research Articles

Targeted colorectal cancer treatment: In vitro anti-cancer effects of carnosine nanoparticles supported by agar and magnetic iron oxide

The usage of peptides in the colorectal cancer (CRC) treatment promises to be a new anti-cancer therapy with improved treatment efficacy. Carnosine, a natural dipeptide molecule, has been demonstrated to be a potential anti-cancer drug. Nonetheless, it shows an exhibition of high-water solubility and is quickly degraded by carnosinase. Meanwhile, agar and magnetic iron oxide are the most used materials for drug delivery due to some of their advantages such as the low cost and the larger biocompatibility feature. The purpose of this study was to investigate the anti-cancer ability of agar-encapsulated carnosine nanoparticles (AgCa-NPs) and agar-encapsulated carnosine nanoparticles-coated magnetic iron oxide nanoparticles (AgCaN-MNPs) in human CRC cells, HCT-116. We evaluated the effects of AgCa-NPs and AgCaN-MNPs with a variety of concentrations (0, 5, 10, 15, 30, 40, or 50 mM) on HCT-116 cells after 72 h and 96 h by using MTT assay and observation cell morphology. We then analyzed the cell cycle progression and assessed the expression changes of genes related to apoptosis, autophagy, necroptosis, and angiogenesis after treatment for 96 h. The results showed that AgCa-NPs and AgCaN-MNPs in vitro study decreased HCT-116 cells viability. This effect was attributed to arrest of cell cycle, induction of programmed cell death, and suppression of angiogenesis by AgCa-NPs and AgCaN-MNPs. These findings revealed the antitumor efficacy of AgCa-NPs or AgCaN-MNPs for CRC treatment.

Retention mechanisms of dipeptides on superficially porous particle vancomycin- and teicoplanin-based chiral stationary phases

Chromatographic behavior of new chiral stationary phases (CSPs) Chiral-T and Chiral-V with teicoplanin and vancomycin antibiotics grafted onto superficially porous silica particles was studied in relation to dipeptide (DP) stereoisomers. The unbuffered water–methanol solutions were used as mobile phases (MPs). The effects of physical properties and molecular structure of analytes and selectors on retention and separation of DP stereoisomers are discussed herein. Chiral-T was evinced to exhibit high enantioselectivity, with highest α values attaining 16.5, 18.8 and 20.4 for Gly-Leu, dd/ll-Phe-Leu and ld/dl-Ala-Ala. At this point, Chiral-V did not exhibit enantioselectivity towards DP stereoisomers. The effect of MP composition on retention and enantioseparation of DPs was investigated. Lipophilicity of DPs was found to be an essential factor in the dependence of their retention vs. methanol concentration in МPs. Lipophobic DPs were eluted more quickly by water-rich solvents, with lipophilic DPs exhibiting an asymmetric U-shaped, or a descending dependence of retention factor vs. the methanol percentage on Chiral-T or Chiral-V, respectively. A theoretical model taking into account interaction of both solvents of a binary MP with both an analyte and adsorption sites was successfully applied so as to approximate and interpret the dependences of DP retention (monotonic and U-shaped) vs. a modifier content in MP. Water molecules were evinced to predominantly participate in competitive adsorption with DP molecules. The model predicted better solvation of lipophilic DPs by methanol and better solvation of lipophobic DPs by water. An attempt was made to verify the possibility of modeling by molecular docking the processes occurring during interaction between DP stereoisomers and CSPs, including consideration of the influence of competitive binding of eluent molecules in selector cavity.

Self-assembled dipeptide grafted nanohybrid material strips for reliable spectroscopic and electrochemical recognition of tryptamine

According to the World Health Organization (WHO), foods high in tryptamine may cause foodborne diseases and abnormal activity in the central nervous system (CNS). The real-time monitoring of tryptamine levels is an emphasized topic among scientific community. In the present work, we report a cost-effective fluorescent paper strips-based methodology impregnated with self-assembled dipeptide-modified (DM1) zinc oxide (ZnO) i.e.DM1@ZnO for the real-time monitoring of tryptamine levels. It is based on an organic-inorganic nanohybrid material of self-assembled N-functionalised dipeptide molecule coated over the surface of ZnO thus tailoring its properties for the detection of tryptamine employing spectroscopic and electrochemical methods. The designed material exhibited a noteworthy response towards tryptamine irrespective of the presence of other biogenic amines (BAs). It selectively displayed blue fluorescence under the 365 nm UV light. On top of that, the detection of tryptamine was also corroborated by its transition to 2-oxytryptamine, as deduced from its electrochemical route. Thus, the proposed paper strip-based methodology unbolts a realistic platform for the efficient recognition of varying levels of tryptamine thus tackling the prima facie reasons for foodborne diseases.

Improving the Efficiency and Stability of MAPbI3 Perovskite Solar Cells by Dipeptide Molecules.

Passivating the electronic defects of metal halide perovskite is regarded as an effective way to improve the power conversion efficiency (PCE) of perovskite solar cells (PVSCs). Here, a series of dipeptide molecules with abundant ─C═O, ─O─ and ─NH functional groups as defects passivators for perovskite films are employed. These dipeptide molecules are utilized to treat the surface of prototype methyl ammonium lead iodide (MAPbI3) films and the corresponding PVSCs exhibit enhanced photovoltaic performance and ambient stability, which can be ascribed to: 1) the ─C═O and ─O─ can interact with the undercoordinated Pb2+ ions and the ─NH groups can form hydrogen bonds with the I- ions, passivating the defects in perovskite film and reducing charge recombination in PVSCs; 2) the long alkyl chain of dipeptide molecules increases the hydrophobicity of the perovskite surface and thus enhance the stability of PVSCs. The passivated MAPbI3-based PVSCs exhibit a champion PCE of 20.3% and retain 60% of the initial PCE after 1000h. It is believed that the defects passivation engineering using polypeptide moleculars can be applied in other perovskite compositions for high device efficiency and stability.

Cyclization of alanyl-valine dipeptides in the solid state. The effects of molecular radiator and heat capacity.

Heating of linear dipeptides above a critical temperature initiates their cyclization even in the solid state. This method of obtaining cyclic dipeptides meets the requirements of "green chemistry", provides a high yield of the main product and releases only water as a by-product of the reaction, and does not require solvents. However, to date, the cyclization of only a small number of dipeptides in the solid state has been studied, and some correlations of the process were discovered. The influence of the structure of dipeptide molecules and their crystal packing on the kinetics of solid-state cyclization is still not fully understood. In this work, the cyclization of L-alanyl-L-valine in the solid state upon heating was studied. Using non-isothermal kinetic approaches, the kinetic parameters of this reaction and the optimal kinetic model describing this process were determined. The effect of the features of the crystal packing of dipeptides and their heat capacity on the temperature of the cyclization in the solid state was analyzed. This study expands our knowledge about solid-state reactions involving dipeptides and the ability to control such reactions.

A new insight into the mechanism of solid-state cyclization of dipeptides: The effect of the sequence of amino acid residues in phenylalanyl-leucine and leucyl-phenylalanine

Heat treatment of linear dipeptides in the solid state is a good strategy for obtaining their cyclic analogs with a high yield and minimal costs. However, the cyclization of dipeptides under the crystal lattice constraints is still poorly understood. In this work, the thermally induced cyclization of l-phenylalanyl-l-leucine and l-leucyl-l-phenylalanine in the solid state was studied. Kinetic parameters of these reactions were estimated using the approaches of nonisothermal kinetics. For the first time, a possible mechanism of the reaction and rate-determining step is discussed. The effect of the sequence of amino acid residues in the dipeptide molecules on temperature and activation energy of solid-state cyclization was observed. The optical purity of the reaction products was estimated. The effect of temperature on the state of dipeptides films was visualized using atomic force microscopy. The results obtained contribute to the understanding of the mechanisms of solid-state cyclization of dipeptides and can be useful in the development of methods for the synthesis of diketopiperazine derivatives.

Self-assembled and Zn(II)-coordinated dipeptide nanoparticles with membrane-rupturing action on bacteria.

Metal ion-coordinated self-assembled short-chain amino acid peptide molecules with multi-photon excitation wavelengths and their photoluminescence properties are advantageous for fluorescence-based diagnostics and treatments of biological diseases based on their extra features of antibacterial agents. We have designed a novel strategy based on tryptophan molecule coordinated with Zn(II) ions in the form of biocompatible spherical nanoparticles of diameter 30-80nm which have been used for antibacterial treatments against different kinds of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, and Pseudomonas). Preferably, we have used tryptophan-phenylalanine (Trp-Phe), a dipeptide molecule having tryptophan as principal material against E. coli strains as antimicrobial agents for surface rupturing and killing purposes. Furthermore, based on single amino acid, tryptophan, self-assembled and Zn(II)-coordinated dipeptide nanoparticles (Zn-DPNPs) were studied against three types of multi-drug-resistant bacteria as an active antimicrobial agent. These antibacterial efficient nanoparticles may have best alternative of antibiotic drugs for clinical applications. The capability of self-assembled fluorescence behavior of Zn-coordinated dipeptide molecules and higher hydrophobicity against bacterial cell wall will perform as antimicrobial fluorescent agents. KEY POINTS: • Zn(II) and Cu(II) better coordinated into self-assembled NPs. • Fluorescence signals showed interaction of NPs with gram-ve cell wall. • Significant surface-damaging effects were observed in the case of Cu-DPNPs and Zn-DPNPs.

Crystal structure, vibrational and chemical properties and phase transitions in Glycyl-DL-Aspartic acid and Glycyl-DL-Aspartic acid monohydrated.

In this paper, the structural and vibrational analysis of the dipeptides glycyl-DL- aspartic acid hydrate (H-Gly-DL-Asp-OH.H2O) crystal, with P1¯ (C11) triclinic symmetry and glycyl-DL- aspartic acid (H-Gly-DL-Asp-OH) crystal, with Cc space group (Cs4) monoclinic structure, were studied. The crystallographic structures of these molecules were determined by single-crystal X-ray diffraction. Changes in the powder X-ray diffraction patterns of H-Gly-DL-Asp-OH.H2O as a function of the temperature were recorded. After 403 K, the water molecule detaches itself from H-Gly-DL-Asp-OH.H2O, causing its symmetry to change from triclinic to monoclinic. The normal modes of vibration were analyzed through calculations based on Density Functional Theory (DFT) using the B3LYP functional with the Gaussian bases 6–311++G (d,p) and potential energy distribution (PED) analysis. These results, together with literature data and Raman and infrared (IR) spectroscopy measurements, allowed the identification of the various vibrational normal modes. Furthermore, the effect of high pressure on H-Gly-DL-Asp-OH.H2O was studied by Raman spectroscopy experiments. The results obtained from the Raman spectra at high pressures indicate changes around 2.1 and 4.5 GPa, such as the disappearance, splitting and emergence of some modes, as well as discontinuities in the evolution of wavenumbers of several normal modes of vibration. Such changes involved modes localized in the region of external modes, while others involved molecular backbone modes and modes that participate in hydrogen bonding. The changes were related to small conformational changes associated with H bonds and small deformations in hydrated dipeptide molecules.

Molecular dynamics study of low molecular weight gel forming salt-triggered dipeptide

Molecular dynamics simulation method was used to study the aggregation of Na and Ca salts in different concentrations of Naphthalene-dipeptide (2NapFF) solutions. The results show that high-valence Ca2+ triggers the formation of a gel at a certain dipeptide concentration, and the low-valence Na+ system follows the aggregation law of general surfactants. The results also show that hydrophobic and electrostatic forces are the main driving forces for the formation of dipeptide aggregates, and that hydrogen bonds do not play a major role in the formation of dipeptide solution aggregates. Hydrophobic and electrostatic effects are the main driving forces for the formation of gels in dipeptide solutions triggered by Ca2+. Electrostatic attraction drives Ca2+ to form a weak coordination with four oxygen atoms on two carboxyl groups, which causes the dipeptide molecules to form a gel with a branched network structure.

Minimalistic Artificial Catalysts with Esterase-Like Activity from Multivalent Nanofibers Formed by the Self-Assembly of Dipeptides.

Imitating and incorporating the multiple key structural features observed in natural enzymes into a minimalistic molecule to develop an artificial catalyst with outstanding catalytic efficiency is an attractive topic for chemists. Herein, we designed and synthesized one class of minimalistic dipeptide molecules containing a terminal -SH group and a terminal His-Phe dipeptide head linked by a hydrophobic alkyl chain with different lengths, marked as HS-C n+1-His-Phe (n = 4, 7, 11, 15, and 17; n + 1 represents the carbon atom number of the alkyl chain). The His (-imidazole), Phe (-CO2 -) moieties, the terminal -SH group, and a long hydrophobic alkyl chain were found to have important contributions to achieve high binding ability leading to outstanding absolute catalytic efficiency (k cat/K M) toward the hydrolysis reactions of carboxylic ester substrates.

Dipeptides as environmentally friendly CH4 hydrate inhibitors: Experimental and computational approaches

In this study, three dipeptides (Gly-Gly, Ala-Ala, and Ala-Gly) were appraised as environmentally benign hydrate inhibitors for CH4 hydrate using both experimental and computational methods. Their kinetic inhibition performance was experimentally evaluated using a stirred high-pressure autoclave and a non-stirred high-pressure micro-differential scanning calorimeter. The experimental results demonstrated that the three dipeptides functioned well as CH4 hydrate inhibitors. Ala-Gly was found to be the most effective, and its inhibition performance was comparable to that of polyvinylcaprolactam (PVCap), a polymer-based commercial hydrate inhibitor. Snapshots, hydrate counts, F3 and F4 order parameters, displacement magnitude, mean square displacement, and radial distribution functions of each peptide-containing system were examined using molecular dynamics (MD) simulations to reveal the inhibition mechanism of dipeptides. The MD simulations showed that the N-termini of the dipeptides were the key constituents for inhibiting the CH4 hydrate, and the Ala-Gly-containing system had the strongest interaction between dipeptide molecules and CH4 hydrate. The overall results provide a better understanding of nature-derived, environmentally friendly hydrate inhibitors and offer insights into the molecular inhibition mechanism of various potential inhibitors.

Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae

BackgroundCyclic dipeptides are an important class of natural products owing to their structural diversity and biological activities. In fungi, the cyclo-ring system is formed through the condensation of two α-amino acids via non-ribosomal peptide synthetase (NRPS). However, there are few investigations on the functional identification of this enzyme. Additionally, information on how to increase the production of cyclic dipeptide molecules is relatively scarce.ResultsWe isolated the Eurotium cristatum NWAFU-1 fungus from Jing-Wei Fu brick tea, whose fermentation metabolites contain echinulin-related cyclic dipeptide molecules. We cloned the cirC gene, encoding an NRPS, from E. Cristatum NWAFU-1 and transferred it into the heterologous host Aspergillus oryzae. This transformant produced a novel metabolite possessing an l-tryptophan-l-alanine cyclic dipeptide backbone (Cyclo-TA). Based on the results of heterologous expression and microsomal catalysis, CriC is the first NRPS characterized in fungi that catalyzes the formation of a cyclic dipeptide from l-tryptophan and l-alanine. After substrate feeding, the final yield reached 34 mg/L. In this study, we have characterized a novel NRPS and developed a new method for cyclic dipeptide production.ConclusionsIn this study we successfully expressed the E. Cristatum NWAFU-1 criC gene in A. oryzae to efficiently produce cyclic dipeptide compounds. Our findings indicate that the A. oryzae heterologous expression system constitutes an efficient method for the biosynthesis of fungal Cyclic dipeptides.

Pidotimod increases inflammation in wounded zebrafish embryos

Pidotimod (PDT) is a synthetic dipeptide molecule which can improve immune responses in mice and humans, protecting hosts from infection. However, the exact mechanism of protection remains ill-defined. The effect of pidotimod has not yet been investigated in the inflammatory response of zebrafish. In this study, we used tail wound and infection models of zebrafish to study the effect of PDT on inflammation. We found that zebrafish larvae were sensitive to PDT immersion causing toxicity at doses above 50 μg/mL. The tail wound assay showed that PDT increased the recruitment of neutrophils and macrophages to the wound site and promoted the transcription of the pro-inflammatory cytokine il1b. However, we did not observe protection of uropathogenic Escherichia coli or Mycobacterium marinum infected zebrafish larvae following PDT treatment. This study provides a new platform for PDT research, which is worthy of further research to identify further effects of PDT therapy.

Research on the Electronic Properties of Tyrosine Dipeptide Molecule: Evaluation of the First-principles Theory

Research on the Electronic Properties of Tyrosine Dipeptide Molecule: Evaluation of the First-principles Theory

Anti-Cancer Effects of Carnosine-A Dipeptide Molecule.

Background: Carnosine is a dipeptide molecule (β-alanyl-l-histidine) with anti-inflammatory, antioxidant, anti-glycation, and chelating properties. It is used in exercise physiology as a food supplement to increase performance; however, in vitro evidence suggests that carnosine may exhibit anti-cancer properties. Methods: In this study, we investigated the effect of carnosine on breast, ovarian, colon, and leukemic cancer cell proliferation. We further examined U937 promonocytic, human myeloid leukemia cell phenotype, gene expression, and cytokine secretion to determine if these are linked to carnosine’s anti-proliferative properties. Results: Carnosine (1) inhibits breast, ovarian, colon, and leukemic cancer cell proliferation; (2) upregulates expression of pro-inflammatory molecules; (3) modulates cytokine secretion; and (4) alters U937 differentiation and phenotype. Conclusion: These effects may have implications for a role for carnosine in anti-cancer therapy.

Discovering Collective Variables of Molecular Transitions via Genetic Algorithms and Neural Networks.

With the continual improvement of computing hardware and algorithms, simulations have become a powerful tool for understanding all sorts of (bio)molecular processes. To handle the large simulation data sets and to accelerate slow, activated transitions, a condensed set of descriptors, or collective variables (CVs), is needed to discern the relevant dynamics that describes the molecular process of interest. However, proposing an adequate set of CVs that can capture the intrinsic reaction coordinate of the molecular transition is often extremely difficult. Here, we present a framework to find an optimal set of CVs from a pool of candidates using a combination of artificial neural networks and genetic algorithms. The approach effectively replaces the encoder of an autoencoder network with genes to represent the latent space, i.e., the CVs. Given a selection of CVs as input, the network is trained to recover the atom coordinates underlying the CV values at points along the transition. The network performance is used as an estimator of the fitness of the input CVs. Two genetic algorithms optimize the CV selection and the neural network architecture. The successful retrieval of optimal CVs by this framework is illustrated at the hand of two case studies: the well-known conformational change in the alanine dipeptide molecule and the more intricate transition of a base pair in B-DNA from the classic Watson–Crick pairing to the alternative Hoogsteen pairing. Key advantages of our framework include the following: optimal interpretable CVs, avoiding costly calculation of committor or time-correlation functions, and automatic hyperparameter optimization. In addition, we show that applying a time-delay between the network input and output allows for enhanced selection of slow variables. Moreover, the network can also be used to generate molecular configurations of unexplored microstates, for example, for augmentation of the simulation data.

Gas-Induced Phase Transition of Dipeptide Supramolecular Assembly

Gas-Induced Phase Transition of Dipeptide Supramolecular Assembly

Aggregation of the Dipeptide Leu-Gly in Alcohol-Water Binary Solvents Elucidated from the Solvation Structure for Each Moiety.

The aggregation of a dipeptide, l-leucine-glycine (Leu-Gly), at 100 mmol dm-3 has been observed in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)-water and 2-propanol (2-PrOH)-water solvents at various alcohol mole fractions, xA, using the dynamic light scattering technique and molecular dynamics (MD) simulations. Leu-Gly was dissolved into the HFIP solvents at the concentration over the entire xA range, while the dipeptide was not dissolved in the 2-PrOH solvents above xA = 0.6. Interestingly, the MD snapshots showed different shapes of Leu-Gly aggregates in the HFIP and 2-PrOH solvents. A linear-shaped aggregate forms in the former; in contrast, a spherical-shaped aggregate is generated in the latter. The solvation structure of each moiety of Leu-Gly in the HFIP and 2-PrOH solvents was observed using experimental and theoretical techniques,1H and 13C NMR, IR, and 19F-1H HOESY measurements and MD simulations. These results gave us the reasons for the different shapes of Leu-Gly aggregates in both solvents. In the HFIP solvents, most of the moieties of the dipeptide are easily solvated by HFIP. This induces the elongated structure of Leu-Gly, leading to the electrostatic interaction between the N- (NH3+ group) and C- (COO- group) terminals of dipeptide molecules. On the other hand, in the 2-PrOH solvents, water molecules that initially solvate the moieties of Leu-Gly, such as the N- and C-terminals and the peptide linkage, are not easily eliminated even as the xA is close to 0.6. The water molecules can bridge such moieties of Leu-Gly to form spherical-shaped aggregates. The diffusion coefficients of Leu-Gly in both alcohol-water binary solvents were experimentally determined by NMR DOSY to estimate the geometries of the aggregates in the solvents. The sizes of Leu-Gly aggregates obtained by DOSY for both solvent systems were consistent with those estimated from the MD snapshots.

The enthalpies of dilution of some dipeptides in water at 298.15 K

The enthalpies of dilution of glycyl-L-α-alanine, glycyl-L-α-leucine and glycyl-L-glutamine have been measured in water at T = 298.15 K. The experimental results were used to calculate the enthalpic coefficients of the interactions between dipeptides molecules in water based on McMillan–Mayer's model. The values of the interaction parameters were interpreted in terms of the hydrophobic or hydrophilic properties of the amino acid side chins in the examined dipeptide molecules and the influence on their interactions with each other in water.

Catalytic degradation of 4-Nitrophenol and methylene blue by bioinspired polydopamine coated dipeptide structures

In terms of high surface roughness and porous structure, PDOP coated dipeptide structures can be used in adsorption studies through their functional groups. Besides, PDOP coated dipeptide structures decorated with plasmonic nanoparticles have the potential to be used in application areas such as catalysis, drug release. Firstly, the structures obtained as a result of self-assembly in the PDOP coating and silver nanoparticles (AgNPs) decoration process of PDOP coated flower-like peptide structures were examined. Morphological characterization was performed Scanning Electron Microscopy (SEM) method. The structural transformation of the dipeptide was performed Fourier Transform Infrared Spectroscopy method (FTIR). Then, the usage of PDOP coated diphenylalanine (FF) dipeptide bio-inspired materials was decorated with AgNPs, catalysis and adsorption studies were investigated. For this purpose, the conversion of 4-nitrophenol (4NP) molecule to 4-aminophenol (4AP) was carried out rapidly with a low amount (1.5 mg) of bio-inspired peptide structures. Also, the reduction of the methylene blue (MB) molecule was performed. Because of the negative surface charge of the PDOP coated dipeptide molecules, the blue color of the positively charged MB molecules is quickly removed and reduced from the aqueous medium. In this way, it was possible to use an adsorbent to remove and degradation some molecules from the solvent medium, drug carrier for the medicinal applications, and as a scaffold in tissue engineering applications.