Multiple Recognition Sites Research Articles

The HIV-1 Nuclear Export Complex Reveals the Role of RNA in Crm1 Cargo Recognition.

Crm1 is a highly conserved nuclear exportin that transports >1000 human proteins including ribonucleoprotein (RNP) complexes. The interface between Crm1 and RNP cargos is unknown. The HIV regulatory protein, Rev, was one of the first identified cargos for Crm1 and contains a prototypic nuclear export sequence (NES). We present the cryo-electron microscopy structure of the HIV-1 nuclear export complex (Crm1/Ran-GTP and the Rev/RRE RNP). Rev binds at a previously unseen protein-protein binding site that stabilizes a unique Crm1 dimer and positions two NESs within the Crm1 dimer. The orientation of Rev binding positions the RRE within a charged pocket on the inside of the Crm1 toroid, mediating direct RNA-Ran-GTP contacts, highlighting the significant role of the RRE in the interaction. Structure based mutations, combined with cell-based assays, show that Crm1 has multiple distinct cargo recognition sites and explains how Crm1 can recognize a diverse range of protein and RNP cargos.

BioMOF@PAN Mixed Matrix Membranes as Fast and Efficient Adsorbing Materials for Multiple Heavy Metals' Removal.

Heavy metal ions are a common source of water pollution. In this study, two novel membranes with biobased metal-organic frameworks (BioMOFs) embedded in a polyacrylonitrile matrix with tailored porosity were prepared via nonsolvent induced phase separation methods and designed to efficiently adsorb heavy metal ions from oligomineral water. Under optimized preparation conditions, stable membranes with high MOF loading up to 50 wt % and a cocontinuous sponge-like morphology and a high water permeability of 50-60 L m-2 h-1 bar-1 were obtained. The tortuous flow path in combination with a low water flow rate guarantees maximum contact time between the fluid and the MOFs, and thus a high heavy metal capture efficiency in a single pass. The performances of these BioMOF@PAN membranes were investigated in the dynamic regime for the simultaneous removal of Pb2+, Cd2+, and Hg2+ heavy metals from aqueous environments in the presence of common interfering ions. The new composite adsorbing membranes are capable of reducing the concentration of heavy metal pollutants in a single pass and at much higher efficiency than previously reported membranes. The enhanced performance of the mixed matrix membranes is attributed to the presence of multiple recognition sites which densely decorate the BioMOF channels: (i) the thioether groups, deriving from the S-methyl-l-cysteine and (S)-methionine amino acid residues, able to recognize and capture Pb2+ and Hg2+ ions and (ii) the oxygen atoms of the oxamate moieties, which preferentially interact with Cd2+ ions, as revealed by single crystal X-ray diffraction. The flexibility of the pore environments allows these sites to work synergically for the simultaneous capture of different metal ions. The stability of the membranes for a potential regeneration process, a key-factor for the effective feasibility of the process in real life applications, was also evaluated and confirmed less than 1% capacity loss in each cycle.

Interpenetrated In(III)-MOF with Multiple Recognition Sites for Single-Step Ethylene Purification.

An interpenetrated indium(III) metal-organic framework (MOF), NTUniv-73, with a rarely reported tetrameric indium cluster is developed for streamlining ethylene purification from C2 gases. At 298 K, the adsorption capacities exhibited a complete reversal sequence of C2H6 > C2H2 > C2H4. Grand canonical Monte Carlo simulation indicated that the corners in a octahedral cage facilitated the C2H2/C2H4 separation, while the pocket-like aperture situated between adjacent octahedral cages allows for full contact of C2H6. Breakthrough experiments illustrated that NTUniv-73 could yield pure C2H4 in a single step with a productivity of 0.42 mmol g-1.

Lanthanide metal-organic framework-based surface molecularly imprinted polymers ratiometric fluorescence probe for visual detection of perfluorooctanoic acid with a smartphone-assisted portable device

Perfluorooctanoic acid (PFOA) poses a threat to the environment and human health due to its persistence, bioaccumulation, and reproductive toxicity. Herein, a lanthanide metal-organic framework (Ln-MOF)-based surface molecularly imprinted polymers (SMIPs) ratiometric fluorescence probe (Eu/Tb-MOF@MIPs) and a smartphone-assisted portable device were developed for the detection of PFOA with high selectivity in real water samples. The integration of Eu/Tb MOFs as carriers not only had highly stable multiple emission signals but also prevented deformation of the imprinting cavity of MIPs. Meanwhile, the MIPs layer preserved the fluorescence of Ln-MOF and provided selective cavities for improved specificity. Molecular dynamics (MD) was employed to simulate the polymerization process of MIPs, revealing that the formation of multiple recognition sites was attributed to the establishment of hydrogen bonds between functional monomers and templates. The probe showed a good linear relationship with PFOA concentration in the range of 0.02–2.8 μM, by giving the limit of detection (LOD) of 0.98 nM. Additionally, The red-green-blue (RGB) values analysis based on the smartphone-assisted portable device demonstrated a linear relationship of 0.1–2.8 μM PFOA with the LOD of 3.26 nM. The developed probe and portable device sensing platform exhibit substantial potential for on-site detecting PFOA in practical applications and provide a reliable strategy for the intelligent identification of important targets in water environmental samples.

Chitosan-based fluorescent probe for the detection of Fe3+ in real water and food samples

Iron ions play a crucial role in the environment and the human body. Therefore, developing an effective detection method is crucial. In this paper, we report CNS2, a chitosan-based fluorescent probe utilizing naphthalimide as a fluorophore. CNS2 is designed to “quench” its own yellow fluorescence through the specific binding of compounds containing enol structures to Fe3+. Studying the fluorescence lifetime of CNS2 in the presence or absence of Fe3+ reveals that the quenching mechanism is static. The presence of multiple recognition sites on the chitosan chain bound to Fe3+ gave CNS2 rapid recognition (1 min) and high sensitivity, with a detection limit as low as 0.211 μM. Moreover, the recognition of Fe3+ by CNS2 had a good specificity and was not affected by interferences. More importantly, in this study, CNS2 was successfully utilised to prepare fluorescent composite membranes and to detect Fe3+ in real water samples and a variety of food samples. The results show that the complex sample environment still does not affect the recognition of Fe3+ by CNS2. All the above experiments obtained more satisfactory results, which provide strong support for the detection of Fe3+ by the probe CNS2 in practical applications.

Foldaxane-Based Switchable [c2]Daisy Chains.

Artificial molecular muscles are highly attractive in the field of molecular machinery due to their unique properties of contraction and stretching motion. However, the synthesis of molecular muscles poses formidable challenges as it is hindered by undesirable yields and poor selectivity. Herein, we present a procedure for the dynamic assembly of foldaxane-based [c2]daisy chains, wherein the hermaphroditic sequences consisting of aromatic helices and peptide rods are interlocked through inter-strand hydrogen-bonding interactions. The binding complementarity facilitates a selective and efficient assembly of [c2]daisy chain structures, inhibiting the creation of by-products. Introducing multiple recognition sites confers the system with contraction and stretching motion actuated by chemical stimuli. The rate of this muscle-like motion is calculated to be 0.8 s-1, which is 107 times faster than that of complex dissociation.

Foldaxane‐Based Switchable [c2]Daisy Chains

AbstractArtificial molecular muscles are highly attractive in the field of molecular machinery due to their unique properties of contraction and stretching motion. However, the synthesis of molecular muscles poses formidable challenges as it is hindered by undesirable yields and poor selectivity. Herein, we present a procedure for the dynamic assembly of foldaxane‐based [c2]daisy chains, wherein the hermaphroditic sequences consisting of aromatic helices and peptide rods are interlocked through inter‐strand hydrogen‐bonding interactions. The binding complementarity facilitates a selective and efficient assembly of [c2]daisy chain structures, inhibiting the creation of by‐products. Introducing multiple recognition sites confers the system with contraction and stretching motion actuated by chemical stimuli. The rate of this muscle‐like motion is calculated to be 0.8 s−1, which is 107 times faster than that of complex dissociation.

Post-synthetic modification of MIL-53(Fe) with Tb3+ and guanosine monophosphate: Construction of a fluorescent dual-target sensor

The development of fluorescence-based multi-target sensing sensors has great potential for applications in food safety monitoring and biomedical analysis. Nevertheless, the intricate design remains a hurdle in the construction of these sensors. Luminescent metal-organic frameworks (LMOFs) are suitable materials for the construction of multi-target fluorescent sensors due to their ability to introduce multiple luminescent centers and specific reaction sites through post-synthetic modification (PSM). In this study, a dual-target fluorescent sensor was fabricated via PSM of MIL-53(Fe) with Tb3+ and guanosine monophosphate (GMP). The Tb-GMP@MIL-53(Fe) sensor, with multiple luminescent centers and specific recognition sites, successfully achieved the detection of hydrogen peroxide (H2O2) and acid phosphatase (ACP) with a limit of detection (LOD) of 0.18 μM and 0.73 U/L, respectively. More significantly, this study demonstrates the potential of post-synthetic modified LMOFs in developing dual/multiple-target fluorescent sensors, expanding the scope of sensor designs for various analytes.

All-in-one strategy to construct bifunctional covalent triazine-based frameworks for simultaneous extraction of per- and polyfluoroalkyl substances and polychlorinated naphthalenes in foods

Per- and polyfluoroalkyl substances (PFASs) and polychlorinated naphthalenes (PCNs) are of growing concern due to their toxic effects on the environment and human health. There is an urgent need for strategies to monitor and analyze the coexistence of PFASs and PCNs, especially in food samples at trace levels, to ensure food safety. Herein, a novel β-cyclodextrin (β-CD) derived fluoro-functionalized covalent triazine-based frameworks named CD-F-CTF was firstly synthesized. This innovative framework effectively combines the porous nature of the covalent organic framework and the host-guest recognition property of β-CD enabling the simultaneous extraction of PFASs and PCNs. Under the optimal conditions, a simple and rapid method was developed to analyze PFASs and PCNs by solid-phase extraction (SPE) based simultaneous extraction and stepwise elution (SESE) strategy for the first time. When coupled with liquid chromatography−tandem mass spectrometry (HPLC−MS/MS) and gas chromatography−tandem mass spectrometry (GC−MS/MS), this method achieved impressive detection limits for PFASs (0.020 −0.023 ng/g) and PCNs (0.016 −0.075 ng/g). Furthermore, the excellent performance was validated in food samples with recoveries of 76.7–107 % (for PFASs) and 78.0–108 % (for PCNs). This work not only provides a simple and rapid technique for simultaneous monitoring of PFASs and PCNs in food and environmental samples, but also introduces a new idea for the designing novel adsorbents with multiple recognition sites.

A surface multiple imprinting layers membrane with well-oriented recognition sites for selective separation of chlorogenic acid from Ficus carica L.

Chlorogenic acid (CGA), known as an important natural antioxidative compound in Ficus carica L, has valuable application prospects on health food, functional food, nutrition and dietary formulations. In this study, a surface multiple imprinting layers membrane (SMILM) was developed and applied to separate CGA from F. carica. Two different imprinting layers were integrated onto the membrane surface in sequence. The first imprinting layer was formed by dopamine polymerization and the second imprinting layer was fabricated by atom transfer radical polymerization (ATRP) and boronate affinity. The prepared SMILM with well-oriented multiple recognition sites exhibited high adsorption capacity (52.08 mg·g−1 in 60 min) for CGA and specific selectivity with imprinting factor (IF) of 3.06. Furthermore, the recognition mechanism of SMILM was clarified by molecular simulation and NMR. The SMILM was successfully applied to separate CGA from the fruits, peels and leaves of F. carica with recoveries of 90.22, 83.31 and 84.95 %, respectively.

Unravelling dispersion forces in liquid-phase enantioseparation. Part I: Impact of ferrocenyl versus phenyl groups

BackgroundHighly ordered chiral secondary structures as well as multiple (tunable) recognition sites are the keys to success of polysaccharide carbamate-based chiral selectors in enantioseparation science. Hydrogen bonds (HBs), dipole-dipole, and π-π interactions are classically considered the most frequent noncovalent interactions underlying enantioselective recognition with these chiral selectors. Very recently, halogen, chalcogen and π-hole bonds were also identified as interactions working in polysaccharide carbamate-based selectors to promote enantiomer distinction. On the contrary, the function of dispersion interactions in this field was not explored so far. ResultsThe enantioseparation of chiral ferrocenes featuring chiral axis or chiral plane as stereogenic elements was performed by comparing five polysaccharide carbamate-based chiral columns, with the aim to identify enantioseparation outcomes that could be reasonably determined by dispersion forces, making available a reliable experimental data set for future theoretical studies to confirm the heuristic hypothesis. The effects of mobile phase polarity and temperature on the enantioseparation were considered, and potential recognition sites on analytes and selectors were evaluated by electrostatic potential (V) analysis and molecular dynamics (MD). In this first part, the enantioseparation of 3,3′-dibromo-5,5′-bis-ferrocenylethynyl-4,4′-bipyridine bearing two ferrocenylethynyl units linked to an axially chiral core was performed and compared to that of the analyte featuring the same structural motif with two phenyl groups in place of the ferrocenyl moieties. The results of this study showed the superiority of the ferrocenyl compared to the phenyl group, as a structural element favouring enantiodifferentiation. Significance and noveltyEven if dispersion (London) forces have been envisaged acting in liquid-phase enantioseparations, focused studies to explore possible contributions of dispersion forces with polysaccharide carbamate-based selectors are practically missing. This study allowed us to collect experimental information that support the involvement of dispersion forces as contributors to liquid-phase enantioseparation, paving the way to a new picture in this field.

Effector-dependent structural transformation of a crystalline framework with allosteric effects on molecular recognition ability

Structurally flexible porous crystals that combine high regularity and stimuli responsiveness have received attracted attention in connection with natural allostery found in regulatory systems of activity and function in biological systems. Porous crystals with molecular recognition sites in the inner pores are particularly promising for achieving elaborate functional control, where the local binding of effectors triggers their distortion to propagate throughout the structure. Here we report that the structure of a porous molecular crystal can be allosterically controlled by local adsorption of effectors within low-symmetry nanochannels with multiple molecular recognition sites. The exchange of effectors at the allosteric site triggers diverse conversion of the framework structure in an effector-dependent manner. In conjunction with the structural conversion, it is also possible to switch the molecular affinity at different recognition sites. These results may provide a guideline for the development of supramolecular materials with flexible and highly-ordered three-dimensional structures for biological applications.

Self-powered dual-mode sensing strategy based on graphdiyne and DNA nanoring for sensitive detection of tumor biomarker

MicroRNA-21 (miRNA-21) is currently the only known oncogenic miRNA that is upregulated in almost all malignant tumors and exhibits a broad spectrum of tumor recognition characteristics. It holds significant value in the early diagnosis, malignant degree assessment, and prognostic evaluation of tumors. In this study, a novel dual-mode self-powered sensing platform is developed using Au nanoparticles/graphdiyne as the electrode substrate and combined with DNA nanoring for highly sensitive and specific detection of miRNA-21. The DNA nanoring structure, which is easy to prepare and contains multiple recognition sites, induces significant electrochemical/colorimetric signal responses of the signaling molecule methylene blue. Under optimal conditions, the linear ranges of the electrochemical and colorimetric detection modes of this self-powered sensor are 0.1 fM-100 pM and 0.1 fM-10 nM, respectively, with the detection limits of 35.1 aM and 61.6 aM (S/N=3). This strategy provides a new reference for the sensitive detection of microRNA and has immense potential for application in the screening and detection of clinical nucleic acid diseases.

NeuroCNN_GNB: an ensemble model to predict neuropeptides based on a convolution neural network and Gaussian naive Bayes.

Neuropeptides contain more chemical information than other classical neurotransmitters and have multiple receptor recognition sites. These characteristics allow neuropeptides to have a correspondingly higher selectivity for nerve receptors and fewer side effects. Traditional experimental methods, such as mass spectrometry and liquid chromatography technology, still need the support of a complete neuropeptide precursor database and the basic characteristics of neuropeptides. Incomplete neuropeptide precursor and information databases will lead to false-positives or reduce the sensitivity of recognition. In recent years, studies have proven that machine learning methods can rapidly and effectively predict neuropeptides. In this work, we have made a systematic attempt to create an ensemble tool based on four convolution neural network models. These baseline models were separately trained on one-hot encoding, AAIndex, G-gap dipeptide encoding and word2vec and integrated using Gaussian Naive Bayes (NB) to construct our predictor designated NeuroCNN_GNB. Both 5-fold cross-validation tests using benchmark datasets and independent tests showed that NeuroCNN_GNB outperformed other state-of-the-art methods. Furthermore, this novel framework provides essential interpretations that aid the understanding of model success by leveraging the powerful Shapley Additive exPlanation (SHAP) algorithm, thereby highlighting the most important features relevant for predicting neuropeptides.

Immunoinformatics and MD-simulation data suggest that Omicron spike epitopes are more interacting to IgG via better MHC recognition than Delta variant

BackgroundRecently, in Nov 2021, in South Africa, the SARS CoV-2 variant Omicron was found to be highly infectious and transmissible but with the least fatality. It occupies the nasopharynx-oropharynx and easily spreads. The epidemiological data/reports suggest that several vaccines failed to neutralize Omicron. It has a large number of spike mutations and the RNA/protein vaccines were developed from its predecessors that may justify its escape in most neutralization reactions. Its lower immuno-suppression/cytokine-storming/inflammatory-response effects need exploration. ObjectivesIn the current study, we attempted to delineate the comparative interaction of different variants’ spikes with multiple recognition sites on IgG and HLA-typing of MHC class and I and II. MethodsAll SARS-CoV-2 spike-proteins/human-IgG/MHC-I & II were obtained from the NCBI/ PDB/GISAID database. Initial 3D-structures of the unavailable proteins were constructed by Homology-Modeling (Swissmodel-Expasy) and optimized (PROCHECK). Molecular-docking of spike-IgG/spike- I & MHC-II was performed (HADDOCK2.4/HawkDock) with active-residue screening (CPORT). Antigenicity of epitopes was determined (Vaxigen v2.0-server) and the epitope-model prepared (PEP-FOLD3-server). The binding-affinity/biological-interfaces/visualize were performed (PRODIGY-PyMOL2). We also examined the genesis of feasible transition pathways of functional docked complexes (iMODs) of MHC with different epitopes and antibodies of IgG with different variants. Further, Molecular-Dynamic-Simulation was performed by GROMACS 2023.1 software package. The MD-simulation was run with 100 ns (300 k-heating/1-atm pressure). ResultsSurface-area with interactomes, H-bonding and polar/non-polar bonding were the highest in Omicron spike-IgG interaction. Unlike other variants, both the L and H chains of at least three different recognition sites of IgG interact with the N-terminal and C-terminal RBD of the S1-portion and partially bind to S2. In other cases, binding was observed in either NTD or CTD with a lesser number of bonding-interactomes, especially in Delta spike-Ab interaction. In the case of MHC class-I & II, the highest binding affinity/surface was noticed by Omicron and least by the Delta variant. The MD simulation data of lower RMSD values of the Delta and Omicron variants indicate improved structural stability and less departure from the initial conformation. Better binding to the IgG and MHC molecules explains Omicron’s little ability in immune invasion.

A photoelectrochemical biosensor based on ZnIn2S4@AuNPs coupled with circular bipedal DNA walker for signal-on detection of circulating tumor DNA

The circulating tumor DNA (ctDNA) is a crucial cancer marker, its sensitive monitoring is useful for early diagnose and therapy of tumor-related diseases. Herein, a bipedal DNA walker with multiple recognition sites is designed through the transition of dumbbell-shaped DNA nanostructure to realize the dual amplification of the signal and achieve ultrasensitive photoelectrochemical (PEC) detection of ctDNA. Initially, the ZnIn2S4@AuNPs is obtained by combining the drop coating method with electrodeposition method. When the target is present, the dumbbell-shaped DNA structure transforms into an annular bipedal DNA walker that can walk unrestrictedly on the modified electrode. After the cleavage endonuclease (Nb.BbvCI) was added to the sensing system, the ferrocene (Fc) on the substrate is released from the electrode surface, and the transfer efficiency of photogenerated electron-hole pairs is extremely improved, enabling the “signal on” testing of ctDNA. The detection limit of the prepared PEC sensor is 0.31 fM, and the recovery of actual samples varied between 96.8 and 103.6% with an average relative standard deviation of about 8%. Meaningfully, the prepared PEC biosensor with an innovative bipedal DNA walker has potential application value for ultrasensitive detection of other nucleic acid-related biomarker.

Stepwise Coordination-Driven Metal-Phenolic Nanoparticle as a Neuroprotection Enhancer for Alzheimer's Disease Therapy.

Current therapeutic strategies for Alzheimer's disease (AD) mainly focus on inhibition of aberrant amyloid-β peptide (Aβ) aggregation. However, these strategies cannot repair the side symptoms (e.g., high neuronal oxidative stress) triggered by Aβ accumulation and thus show limited effects on suppressing Aβ-induced neuronal apoptosis. Herein, we develop a stepwise metal-phenolic coordination approach for the rational design of a neuroprotection enhancer, K8@Fe-Rh/Pda NPs, in which rhein and polydopamine are effectively coupled to enhance the treatment of AD in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. We discover that the polydopamine inhibits the aggregation of Aβ oligomers, and rhein helps repair damage to neurons triggered by Aβ aggregation. Based on molecular docking, we demonstrate that the polydopamine has a strong interaction with Aβ monomers/fibrils through its multiple recognition sites (e.g., catechol groups, imine groups, and indolic/catecholic π-systems), thereby reducing Aβ burden. Further investigation of the antioxidant mechanisms suggests that K8@Fe-Rh/Pda NPs promote the mitochondrial biogenesis via activating the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway. This finally inhibits neuronal apoptosis. Moreover, an intravenous injection of these nanoparticles potently improves the cognitive function in APP/PS1 mice without adverse effects. Overall, our work provides a promising approach to develop advanced nanomaterials for multi-target treatment of AD.

Divalent Benzimidazolium-Based Axles for Self-Reporting Pseudorotaxanes.

Mono- and (bis)benzimidazoliums were evaluated both experimentally and computationally for their potential as pseudopolyrotaxane axle building blocks. Their aggregation and photophysical behavior, along with their potential to form a [2]pseudorotaxane with dibenzyl-24-crown-8, was studied through the synergistic application of 1D/2D and diffusion-ordered NMR spectroscopy, mass spectrometry, ultraviolet-visible and fluorescence spectroscopy, and time-dependent density functional theory. Their photophysical behavior was measured and modeled as a function of protonation state, solvent, and concentration. The axles show strong solvochromaticism and a very pronounced concentration-dependent optical profile, including self-quenching when a pseudorotaxane is formed. This axle with multiple recognition sites has the potential to form pseudorotaxanes with tunable optical behavior.

A Review: Using Multiple Templates for Molecular Imprinted Polymer: Is It Good?

A multi-template molecularly imprinting polymer (MT-MIP) strategy has been proposed and is increasingly utilised to synthesise MIP with multiple recognition sites in a single polymer using multiple target species as templates. This approach can expand MIP applications for simultaneous recognition and extraction of more than one analyte. The advantages of MT-MIP are simultaneous analyte extraction in one process, lower solvent consumption, cost-effectiveness, and short analysis time. The use of multiple templates to prepare a MIP reduces the effort required to prepare different MIPs for different analytes separately. Although there are many studies about developing MT-MIP, there are no review articles that discuss the success rate of MT-MIP. Therefore, in this review, we summarise MT-MIP synthesis, including the polymerisation method being used, the important factors that affect the quality of MT-MIP, and MT-MIP applications. MT-MIP has great potential in chemical isolation and analysis. MT-MIP produces a product that has good sensitivity, selectivity, and reusability. Furthermore, many templates, functional monomers, and crosslinkers can be formulated as MT-MIP and have a high success rate. This is evidenced by the good values of the maximum absorption capacity (Qmax), imprinting factor (IF), and reusability. We expect that the evidence presented in this review can encourage additional research on the development and application of MT-MIP.

A biomimetic metal–organic framework with cuboid inner cavities for enantioselective separation

A biomimetic metal–organic framework with cuboid inner cavities and multiple recognition sites was constructed from a phenylalanine-derived ligand. It can enantioselectively separate various racemic alcohols, diols and epoxides with ee up to 99.5%.