Similar Biomolecules Research Articles

Conformational Landscape of NADH and Ion Binding in Water/DMSO Mixtures via 31P NMR Spectroscopy.

This study reports on the conformational states of nicotinamide adenine dinucleotide (NADH) in water/DMSO mixtures and examines the influence of ion binding. We observe evidence of conformational changes through a series of NMR techniques, including 31P NMR relaxation (R1 and R2), chemical exchange saturation transfer (CEST), and diffusion-ordered spectroscopy (DOSY) experiments. The observed variation of the conformational states is indicative of the solvent's influence on NADH's structural flexibility. The experimental findings, in combination with viscosity data, are shown to be in line with findings from earlier molecular dynamics studies. The reported observations emphasize the critical role of the solvent environment in determining the conformational states of NADH and similar molecules with relevance for the biophysiological context. The results found herein can help in studying the biophysical behavior of NADH and similar biomolecules and their associated metabolic pathways under various solvent conditions.

WUREN: Whole-modal union representation for epitope prediction

B-cell epitope identification plays a vital role in the development of vaccines, therapies, and diagnostic tools. Currently, molecular docking tools in B-cell epitope prediction are heavily influenced by empirical parameters and require significant computational resources, rendering a great challenge to meet large-scale prediction demands. When predicting epitopes from antigen-antibody complex, current artificial intelligence algorithms cannot accurately implement the prediction due to insufficient protein feature representations, indicating novel algorithm is desperately needed for efficient protein information extraction. In this paper, we introduce a multimodal model called WUREN (Whole-modal Union Representation for Epitope predictioN), which effectively combines sequence, graph, and structural features. It achieved AUC-PR scores of 0.213 and 0.193 on the solved structures and AlphaFold-generated structures, respectively, for the independent test proteins selected from DiscoTope3 benchmark. Our findings indicate that WUREN is an efficient feature extraction model for protein complexes, with the generalizable application potential in the development of protein-based drugs. Moreover, the streamlined framework of WUREN could be readily extended to model similar biomolecules, such as nucleic acids, carbohydrates, and lipids.

Paper-based microfluidic system and chiroptical functionalized gold nano-oval for colorimetric detection of L-Tryptophan

“The development and deployment of a practical and portable technology for on-site chiral identification of enantiomers hold immense significance in the fields of medical and biological sciences. Among the essential amino acids, Tryptophan (Trp) plays a crucial role in human metabolism and serves as a diagnostic marker for various metabolic disorders. In this study, we introduce an innovative approach that combines an enantio-selective ZIF-8-His MOF-MIPs packed-bed centrifugal microfluidic system with an enantioselective colorimetric sensor probe. This system is further integrated with smartphone-based on-site data recording. The basis of this colorimetric sensor's operation lies in the controlled morphology and surface passivation of gold nano-ovals (Au–NOs) through DL-Alanine. To confirm the successful synthesis of the chiral recognition elements, we employed various characterization techniques, including FE-SEM, TEM, FTIR, CD, UV–Vis, zeta potential, DLS, and XRD. Our focus was on optimizing operational parameters for the effective separation and determination of L-chiral tryptophan on-site. The sensor exhibited two linear ranges for L-Trp detection: 0–5.42 and 5.42–80.47 mM, with a detection limit of 0.5 mM. The integrated system possesses advantages such as ease of availability, preparation, high stability, desirable selectivity even in the presence of similar biomolecules, and rapid detection capabilities. Furthermore, our method demonstrated successful enantioselective sensing of L-Trp in various biological samples, including human blood plasma, urine, milk, and bovine serum albumin (BSA), yielding promising results. The integrated microfluidic platform follows a "sample-in and answer-out" approach, making it highly applicable in healthcare, environmental monitoring, food safety analysis, and point-of-care testing. The chiral recognition pretreatment assay and self-contained, automated colorimetric detection on the microfluidic disc represent a promising avenue for cutting-edge research in these domains”.

Microfluidic chip and chiroptical gold nanoparticle-based colorimetric sensor for enantioselective detection of L-tryptophan

Herein, we introduce a novel integrated system that merges an enantio-discriminative bio-MOF-packed centrifugal microfluidic chip made from PDMS with a user-friendly on-site colorimetric sensor. This innovative approach enables the precise enantioselective recognition of L-tryptophane (L-Trp). This chiral recognition probe was successfully synthesized through meticulous control of nano-ovals-shaped gold nanoparticles morphology and surface passivation. The operational factor of this methodology was optimized to ensure simplicity, practicality, and efficiency. This optimization led to reduced reagent consumption and instantaneous analytical feedback. The integrated system was effectively applied for enantioselective separation and quantification of L-Trp across an extensive linear range of 50 μM-1.5 mM, impressive limit of detection as low as 15 μM. It is noteworthy that this integrated system demonstrated desirable selectivity even in the presence of similar biomolecules, showcasing its robust performance and rapid detection capability. Further extended the application of this strategy to exceptional performance across enantioselective sensing of L-Trp in various sample matrices, comprising bovine serum albumin, bovine milk, blood plasma and urine samples. This integrated microfluidic sample pretreatment, chiroptical sensing, and on-site signal recording with a smartphone hold tremendous potential for widespread implementation, practical applications engaging healthcare and environmental, food safety, and point-of-needs analysis, facilitating successive solution mixing and colorimetric detection.

Photo-responsive oxidase-like nanozyme based on a vanadium-docked porphyrinic covalent organic framework for colorimetric L-Arginine sensing.

This study reports the development of a vanadium-docked porphyrinic covalent organic framework as a novel class of highly polar photoactive materials. Thanks to its extended π-electron conjugation and high chemical stabilities, this framework can serve as an oxidase-Like photo-nanozyme for photocatalytic oxidation of o-phenylenediamine (o-PDA) and a colorimetric substrate for the production of the yellow-colored oxidized o-PDA (o-PDAox). The physicochemical properties of the as-prepared photo-nanozyme were characterized by several analytical techniques. Its enhanced light harvesting and charge separation and transfer were also verified by electrochemical and spectroscopic analysis. This photo-nonenzymatic colorimetric assay was applied for the sensitive L-Arginine (L-Arg) detection as a typical amino acid in the linear range of 8.1nM-330 μM with a limit of detection (LOD) of 3.5nM. The findings of this research confirmed the safety and feasibility of the proposed photo-nonenzymatic colorimetric sensing strategy for the detection of L-Arg and other similar biomolecules in food samples. Kinetic investigation revealed that the photo-responsive oxidase mimic exhibits satisfactory Km (0.47mM) and Vmax (42.0μM/s) values. This work broadened our insight into the development of modified porphyrinic-COF-based visible light-responsive oxidase-like photo-nanozyme for environmentally friendly colorimetric biosensing.

Interplay of Near-Zero-Field Dephasing, Rephasing, and Relaxation Dynamics and [1-13C]Pyruvate Polarization Transfer Efficiency in Pulsed SABRE-SHEATH.

Hyperpolarized [1-13C]pyruvate is a revolutionary molecular probe enabling ultrafast metabolic MRI scans in 1 min. This technology is now under evaluation in over 30 clinical trials, which employ dissolution Dynamic Nuclear Polarization (d-DNP) to prepare a batch of the contrast agent; however, d-DNP technology is slow and expensive. The emerging SABRE-SHEATH hyperpolarization technique enables fast (under 1 min) and robust production of hyperpolarized [1-13C]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes. Here, we study the application of microtesla pulses to investigate their effect on C-13 polarization efficiency, compared to that of conventional SABRE-SHEATH employing a static field (∼0.4 μT), to provide the matching conditions of polarization transfer from parahydrogen-derived hydrides to the 13C-1 nucleus. Our results demonstrate that using square-microtesla pulses with optimized parameters can produce 13C-1 polarization levels of up to 14.8% (when detected, averaging over all resonances), corresponding to signal enhancement by over 122,000-fold at the clinically relevant field of 1.4 T. We anticipate that our results can be directly translated to other structurally similar biomolecules such as [1-13C]α-ketoglutarate and [1-13C]α-ketoisocaproate. Moreover, other more advanced pulse shapes can potentially further boost heteronuclear polarization attainable via pulsed SABRE-SHEATH.

ZIF-8 Nanoparticles Based Electrochemical Sensor for Non-Enzymatic Creatinine Detection.

There is a consistent demand for developing highly sensitive, stable, cost-effective, and easy-to-fabricate creatinine sensors as creatinine is a reliable indicator of kidney and muscle-related disorders. Herein, we reported a highly sensitive and selective non-enzymatic electrochemical creatinine sensor via modifying poly(3,4 ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) coated indium tin oxide (ITO) substrate by zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs). The topography, crystallinity, and composition of the sensing electrode were characterized by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The peroxidase-like activity of ZIF-8 nanoparticles enabled it to detect creatinine forming a zinc-creatinine composite. The electrochemical behavior and sensing performance were evaluated by amperometric and impedimetric analysis. The sensor obtained a sufficiently low limit of detection (LOD) of 30 µM in a clinically acceptable linear range (0.05 mM–2.5 mM). The interference study demonstrated high selectivity of the sensor for creatinine concerning other similar biomolecules. The sensing performance of the creatinine sensor was verified in the actual human serum, which showed excellent recovery rates. Hence, the magnificent performance of ZIF-8 based non-enzymatic creatinine sensor validated it as a responsible entity for other complicated renal markers detection.

Selectivity and Targeting of G-Quadruplex Binders Activated by Adaptive Binding and Controlled by Chemical Kinetics.

G-quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4-DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF-G4 (a promoter G4) shows that Pt1 matches 3'-G-tetrad of VEGF-G4 through Cl- -dissociation and loop rearrangement of VEGF-G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate-determining binding step, Cl- -dissociation upon G4-binding, is 2-3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4-binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.

Selectivity and Targeting of G‐Quadruplex Binders Activated by Adaptive Binding and Controlled by Chemical Kinetics

AbstractG‐quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4‐DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF‐G4 (a promoter G4) shows that Pt1 matches 3′‐G‐tetrad of VEGF‐G4 through Cl−‐dissociation and loop rearrangement of VEGF‐G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate‐determining binding step, Cl−‐dissociation upon G4‐binding, is 2–3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4‐binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.

Nanoparticles induce the biosynthesis and activity of the new possible therapeutic proteinase source, Talaromyces purpureogenus KJ584844

The need for the bacterial proteinase is rapidly growing, urging to catch a lowcost medium for the microbial fermentation, nanoparticles can play a vital role in this respect. The proteinase of Talaromyces purpureogenus was produced on the tubers of Helianthus tuberosus that also operated as solid support for the fermentation process. The interface amongst nitrogen sources (NH4Cl and yeast extract) was investigated, applying the statistical modeling of central composite design under solid-state fermentation. The optimum medium for proteinase secretion was stimulated by 979.82 mg NH4Cl and 437.68 mg yeast extract per 100 g substrate, yielding 108.15 U/g tubers. Using Plackett-Burman experimental design, the nanoparticles Co, Ni and Fe were assessed as inducers for proteinase stimulants. Co nanoparticles (5 ppm) were the greatest in both proteinase production by the fungus as well as an inducer of the proteolysis process by the enzyme when using faba bean straw as a proteinaceous substrate in the reaction mixture, liberating the extreme quantity of amino acids, compared with the lack of the nanoparticles. The findings suggest the incorporation of Co nanoparticles in both the proteinase fabrication process and during the degradation of proteinaceous materials induce proteinase catalyst. This approach could be extended to modulate the productivity and activity of similar biomolecules.

Highly fluorescent water-soluble PTCA incorporated silver nano-cluster for sensing of dopamine

In the present work, we designed a novel nanocluster (PTCA/Capt-AgNC) with a remarkably enhanced fluorescence, photostability and water solubility. This green fluorescent nanocluster with dimension of ~ 2–4 nm was characterized by UV–Vis, Fourier transformed infrared, Raman, photoluminescence (PL) spectroscopies; X-ray diffraction (XRD), high resolution transmission electron microscopy and selected area electron diffraction techniques. It was observed that the incorporation of a tiny amount of 3,4,9,10-perylene tetracarboxylic acid (PTCA) into captopril (Capt) protected silver nanocluster (Capt-AgNCs) resulted in the increase of PLQY by several orders of magnitude compared to PTCA and Capt-AgNCs. The PL studies indicated that the material has high photoluminescence quantum yield (PLQY ~ 0.25) in comparison to the previously reported Capt-AgNCs. Fluorescence intensity of PTCA/Capt-AgNCs was quenched upon addition of various concentrations of dopamine. Selectivity in fluorescence quenching was evaluated with structurally similar bio-molecules such as l-cysteine and urea. Time resolved fluorescence spectroscopy revealed that the average fluorescence lifetime of the nanocluster was reduced strikingly upon addition of dopamine in comparison to that with l-cysteine and urea which clearly indicated the selectivity and sensitivity. Density functional theory calculations were performed to investigate the PL enhancement and quenching mechanisms. We believe that strategy reported in the present study could be adopted for designing highly efficient biosensors.

FRET-Based Aptasensor for the Selective and Sensitive Detection of Lysozyme.

Lysozyme is a conserved antimicrobial enzyme and has been cited for its role in immune modulation. Increase in lysozyme concentration in body fluids is also regarded as an early warning of some diseases such as Alzheimer’s, sarcoidosis, Crohn’s disease, and breast cancer. Therefore, a method for a sensitive and selective detection of lysozyme can benefit many different areas of research. In this regard, several aptamers that are specific to lysozyme have been developed, but there is still a lack of a detection method that is sensitive, specific, and quantitative. In this work, we demonstrated a single-molecule fluorescence resonance energy transfer (smFRET)-based detection of lysozyme using an aptamer sensor (also called aptasensor) in which the binding of lysozyme triggers its conformational switch from a low-FRET to high-FRET state. Using this strategy, we demonstrated that the aptasensor is sensitive down to 2.3 picomoles (30 nM) of lysozyme with a dynamic range extending to ~2 µM and has little to no interference from similar biomolecules. The smFRET approach used here requires a dramatically small amount of aptasensor (~3000-fold less as compared to typical bulk fluorescence methods), and it is cost effective compared to enzymatic and antibody-based approaches. Additionally, the aptasensor can be readily regenerated in situ via a process called toehold mediated strand displacement (TMSD). The FRET-based aptasensing of lysozyme that we developed here could be implemented to detect other protein biomarkers by incorporating protein-specific aptamers without the need for changing fluorophore-labeled DNA strands.

Release of sugars and fatty acids from heavy oil biodegradation by common hydrolytic enzymes

In response to recent advances in understanding relating to the remarkable persistence of soil organic matter during burial and diagenesis, we examine the extent to which bitumen compositionally reflects the soil organic matter from which it was derived. Through a simple set of experiments, exposure of bitumen to lipase and cellulase, two enzymes effective in the biodegradation of soil organic matter, resulted in the release of glycerin, palmitic and oleic fatty acids from lipase digestion in addition to the release of glucose, alkylphenols and acyclic polyols from fermentation with cellulase, consistent with the products expected these enzymes. These results are significant in that they suggest that heavy oils are more similar to their soil precursor than previously thought, that biodegradation of bitumen can be accelerated using common over the counter enzymes in aerobic conditions and that heavy oils, which are 1000 times more abundant than coal, can release similar biomolecules as those generated in bioreactor culture or biomass harvest, using two of the most abundantly produced enzymes presently available.

Evaluation of the efficiency of nanoadsorbent derived from orange peels in the removal of cerium from aqueous solution

The use of biomass as low cost and eco-friendly adsorbent has been investigated as alternative to current chemically synthesized media, which are used for the removal of toxic metals from wastewater. The effectiveness of nano-adsorbents obtained from orange (ORN) peels in the adsorption of cerium from simulated water has been studied. The nano-adsorbent were characterized by Brunauer–Emmett–Teller, Fourier transform infrared and transmission electron microscopy analyses. Analyses revealed that ORN exhibited narrow particle size distribution (4–50 nm), spherical morphology and enhanced surface area. The functional group found to be responsible for the coordination and removal of the metal ion was mainly the carboxyl group. The adsorption performance was studied as a function of adsorbent dosage, initial concentration, solution pH and temperature. The results were compared with banana peels nano-adsorbent (BPN), which contained similar biomolecules to ORN. In both samples, the adsorption process followed Langmuir isotherm model with the capacity of 45.2 mg g−1 for the ORN and 35.9 mg g−1 for BPN. The higher performance achieved using ORN might be due to the smaller particle size and higher surface area of ORN compared to the BPN. The results obtained indicated that nanostructured agricultural wastes could be potential adsorbents for Ce removal from wastewater.

Propanol – Sugar aqueous biphasic systems as a suitable platform for biomolecules extraction

Aiming at designing efficient extraction processes, this work proposes the novel aqueous biphasic systems (ABS) composed of sugars and alcohols. The complete liquid-liquid phase diagrams (binodal curves and tie-lines) for several ternary systems of {water + 1-propanol / 2-propanol + sugar (mono- and di-saccharides, and their polyols)} were determined, for the first time. The main factors which affect the phase separation ability of these systems, such as temperature, structure and stereochemistry of sugars, and the alcohol type were discussed. In all the studied ABS, the top phase is alcohol-rich with lower water content, while the bottom phase is sugar-rich with higher water content. The partitioning behavior of two alkaloids (caffeine and codeine) and a flavoring antioxidant (vanillin) in the produced ABS was evaluated. In all the partitioning experiments, caffeine and vanillin have a preferable tendency to concentrate in the more hydrophobic alcohol-rich phase, however, codeine preferentially migrate to the more hydrophilic sugar-rich phase. The selectivity index of the alcohol-sugar ABS to separate compounds of the same family (caffeine and codeine) was calculated and found to be higher than 25 at optimum conditions. In general, the more soluting-out ability of sugars, the more difference in the water content of the coexisting phases, and the longer tie-line length lead to the better extraction performance of the propanol-sugar ABS. Heating has a favorable effect on the preferential partitioning of caffeine and codeine, but it is unfavorable for extraction of vanillin. From the results gathered, the novel ABS produced in this work provide efficient and money-saving extraction platforms, and can selectively separate similar biomolecules.

A wide-color-varying ratiometric nanoprobe for detection of norepinephrine in urine samples

Owing to its dual role as a hormone and neurotransmitter, norepinephrine (NE) detection is of great significance to biomedical diagnosis. In the present work, we have explored intense green fluorescence of poly (norepinephrine) (PNE) nanoparticles synthesized by oxidizing NE in alkaline condition, in combination with red fluorescent bovine serum albumin-stabilized gold nanoclusters (BSA-AuNCs) for naked-eye detection of NE. The effect of sodium hydroxide on the emission behavior of NE was studied. The surface morphology and optical properties of PNE nanoparticles were characterized by UV–Vis, fluorescence, FTIR, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) techniques. For ratiometric sensing of NE, red fluorescent BSA-AuNCs were served as an internal reference while NE delivered a new emission peak at 527 nm, resulting in a wide distinguishable color change from strong red into red, pink, orange, and green under a UV lamp. The ratiometric approach was demonstrated to be highly sensitive and selective for NE detection against even structurally similar biomolecules with a detection limit of 49 nmol L−1. Furthermore, the proposed method was successfully applied to determine NE in urine samples.

Potential of Aqueous Two-Phase Systems for the Separation of Levodopa from Similar Biomolecules.

Levodopa is a precursor of several neurotransmitters, such as dopamine, and is used in the treatment of the Parkinson's disease. In this work, an alternative strategy was studied to separate levodopa from similar biomolecules using aqueous two-phase systems (ATPS). Ternary ATPS composed of polyethylene glycol (PEG) 400 or ionic liquids (ILs), citrate buffer (K3C6H5O7/C6H8O7) at pH 7.0 and water, and quaternary ATPS composed of PEG 400, K3C6H5O7/C6H8O7 at pH 7.0, water and the same ILs at 5 wt%, were studied. The respective liquid-liquid phase diagrams were determined at 298 K to appraise the mixture compositions required to form two-phase systems, followed by studies of the partition of levodopa and structurally similar biomolecules (dopamine, L-phenylalanine, and L-tyrosine). Their partition coefficients and extraction efficiencies have been determined, and the selectivity of the ATPS to separate levodopa from the remaining biomolecules evaluated. The results obtained indicated that PEG-based ATPS were the most effective to separate levodopa from L-phenylalanine while the separation from the other biomolecules was better using IL-based ATPS, in particular those based on [P4444]Cl and [N4444]Cl, with extraction efficiencies of levodopa to the salt-rich phase ranging between 62.7 and 74.0%, and of the remaining biomolecules to polymer/IL-rich phase up to 91.5%.

Performance of a High-Pressure Liquid Chromatography-Ion Mobility-Mass Spectrometry System for Metabolic Profiling.

A commercial liquid chromatography/drift tube ion mobility-mass spectrometer (LC/IM-MS) was evaluated for its utility in global metabolomics analysis. Performance was assessed using 12 targeted metabolite standards where the limit of detection (LOD), linear dynamic range, resolving power, and collision cross section (Ω) are reported for each standard. Data were collected in three different instrument operation modes: flow injection analysis with IM-MS (FIA/IM-MS), LC/MS, and LC/IM-MS. Metabolomics analyses of human plasma and HaCaT cells were used to compare the above three operation modes. LC/MS provides linearity in response, data processing automation, improved limits of detection, and ease of use. Advantages of LC/IM-MS and FIA/IM-MS include the ability to develop mobility-mass trend lines for structurally similar biomolecules, increased peak capacity, reduction of chemical/matrix noise, improvement in signal-to-noise, and separations of isobar/isomer compounds that are not resolved by LC. We further tested the feasibility of incorporating IM-MS into conventional LC/MS metabolomics workflows. In general, the addition of ion mobility dimension has increased the separation of compounds in complex biological matrixes and has the potential to largely improve the throughput of metabolomics analysis.

ChemInform Abstract: Thiazolo[4,5‐d]pyrimidines as a Privileged Scaffold in Drug Discovery

AbstractReview: 74 refs.

The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths.

The proposed AIBLHiCoS method predicts a given compound's pKa in aqueous solution from a single ab initio bond length only, after geometry optimization in the gas phase. Here we provide simple and predictive equations for naphthols and chemically similar biomolecules. Each linear equation corresponds to a High-Correlation Subset (HiCoS) that expresses the novel type of linear free energy relationship discovered here. The naphthol family exhibits a clear and strong relationship with the phenol family, with the "active" C-O bond always producing the highest correlations. The proposed method can isolate erroneous experiments and operate in non-aqueous solution and at different temperatures. Moreover, the existence of "active fragments" is demonstrated in a variety of sizable biomolecules for which the pKa is successfully predicted.