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Lys48‐linked ubiquitin chains, regulating proteasomal protein degradation, are known to include cyclized forms. This cyclization hinders recognition by many downstream proteins by occluding the Ile44‐centered patch. In contrast, the A20‐like Znf domain of ZNF216 (a ubiquitin‐binding protein, A20 Znf) is expected to bind to cyclic ubiquitin chains via constitutively solvent‐exposed surfaces. However, the underlying interaction mechanism remains unclear. Here, our ITC and NMR experiments collectively showed that cyclization did not interfere with and even slightly enhance the molecular recognition of diubiquitin by A20 Znf. This effect is explained by the cyclization‐induced repression of conformational dynamics in diubiquitin and an enlarged molecular interface in the complex. Thus, these results suggest that cyclic ubiquitin chains can be involved in regulation of ZNF216‐dependent proteasomal protein degradation. [ABSTRACT FROM AUTHOR]

Recombinant proteins hold significant importance in numerous disciplines. As the demand for expressing and purifying these proteins grows, the scientific community is in dire need of a simple yet versatile methodology that can efficiently purify these proteins. Aptamers as synthetic nucleic acid–based ligands with high affinity have shown promise in this regard, as they can capture targets through molecular recognition. In this study, novel aptamer‐functionalized polydopamine‐coated magnetic graphene oxide nanocomposites were facilely prepared, achieving an impressive average aptamer coverage density (45 nmol/mg). These nanocomposites exhibited a uniform structure and robust magnetic responsiveness. The findings indicated that they possess several advantages, such as rapid adsorption, substantial capacity (171.4 mg/g), and excellent reusability. Notably, due to the inherent properties of nucleic acids, the immobilized aptamer‐magnetic beads can be utilized repeatedly with high purification efficiency. Finally, the nanocomposites were further employed to purify His‐tagged proteins from actual samples. Remarkably, they were able to selectively and efficiently isolate His‐tagged retinoid X receptor alpha protein from complex Escherichia coli lysate. The purified His‐tagged retinoid X receptor alpha protein was analyzed using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. This confirmed the efficacy of developed nanocomposites, reinforcing their vast potential for purification of His‐tagged recombinant proteins. [ABSTRACT FROM AUTHOR]

The enzymatic atroposelective synthesis of biaryl compounds is relatively rare, despite considerable attention received by biocatalysis in the academic and industrial sectors. Imine reductases (IREDs) are an important class of enzymes that have been applied in the asymmetric synthesis of chiral amine building blocks. In this study, two IREDs (IR140 and IR189) were identified to catalyze the efficient desymmetrization of biaryls utilizing various amine donors. Further protein engineering enabled the identification of variants (IR189 M8–M9 and IR189 M13–M14) that are able to catalyze the formation of both (R) and (S) atropisomers in excellent yields and atroposelectivities (24 examples, up to 99 % ee and yield). The absolute configuration and rotational barriers were confirmed, and the reactions were readily scaled up to allow isolation of the atropisomeric product in 99 % ee and 82 % yield. The optically pure biaryl amines were further derivatized into various synthetically useful atropisomers. To shed light on the molecular recognition mechanisms, molecular dynamics (MD) simulations were performed, offering plausible explanations for the improved atroposelectivity and enzymatic activity. The current strategy expands the scope of the IRED‐catalyzed synthesis of axially chiral biaryl amines, contributing significantly to the field of atroposelective biocatalysis. [ABSTRACT FROM AUTHOR]

An on‐going challenge with COVID‐19, which has huge implications for future pandemics, is the rapid emergence of viral variants that makes diagnostic tools less accurate, calling for rapid identification of recognition elements for detecting new variants caused by mutations. We hypothesize that we can fight mutations of the viruses with mutations of existing recognition elements. We demonstrate this concept via rapidly evolving an existing DNA aptamer originally selected for the spike protein (S‐protein) of wildtype SARS‐CoV‐2 to enhance the interaction with the same protein of the Omicron variants. The new aptamer, MBA5SA1, has acquired 22 mutations within its 40‐nucleotide core sequence and improved its binding affinity for the S‐proteins of diverse Omicron subvariants by >100‐fold compared to its parental aptamer (improved from nanomolar to picomolar affinity). Deep sequencing analysis reveals dynamic competitions among several MBA5SA1 variants in response to increasing selection pressure imposed during in vitro selection, with MBA5SA1 being the final winner of the competition. Additionally, MBA5SA1 was implemented into an enzyme‐linked aptamer binding assay (ELABA), which was applied for detecting Omicron variants in the saliva of infected patients. The assay produced a sensitivity of 86.5 % and a specificity of 100 %, which were established with 83 clinical samples. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin‐1 (MUC1) using engineered glycopeptides on nanoparticle probes. We used a structure‐guided approach to develop unnatural glycopeptides as model antigens for tumor‐associated MUC1. We designed a collection of 13 glycopeptides to bind either SM3 or 5E5, two monoclonal antibodies with distinct epitopes known to recognize tumor associated MUC1. Glycopeptide binding to SM3 or 5E5 was confirmed by surface plasmon resonance and rationalized by molecular dynamics simulations. These model antigens were conjugated to gold nanoparticles and used in a dot‐blot assay to detect autoantibodies in serum samples from pancreatic cancer patients and healthy volunteers. Nanoparticle probes with glycopeptides displaying the SM3 epitope did not have diagnostic potential. Instead, nanoparticle probes displaying glycopeptides with high affinity for 5E5 could discriminate between cancer patients and healthy controls. Remarkably, the best‐discriminating probes show significantly better true and false positive rates than the current clinical biomarkers CA19‐9 and carcinoembryonic antigen (CEA). [ABSTRACT FROM AUTHOR]

An engineered tetra‐amide macrocycle is presented, and its conformation and anion recognition properties are investigated. The tetra‐amide macrocycle 1, containing the m‐amino benzoic acid, 1,3‐benzenedicarboxylic acid and m‐xylenedinediamine adopts an envelope‐like conformation in solid‐state, where the m‐xylenedinediamine ring is perpendicular with the molecular plain. The tetra‐amide macrocycle 1 is able to bind anions such as halides, sulphate and phosphate in DMSO (dimethyl sulphoxide) solution. The stabilities of the fluoride (2.6×103 M−1) and chloride (5.6×102 M−1) complexes of 1 in DMSO is higher than that of bromide (66 M−1) and iodide (52 M−1). SO42− complexes of 1 in DMSO is more stable than the HSO4−, NO3− and H2PO4− complexes. Using this information, a quantitative evaluation of the stability of the 1 : 1 complex of 1, for which overall binding energy in the order −123.98 kcal/mol for SO42−was calculated. The strong binding affinity of the tetra‐amide macrocycle 1 toward the SO42− ion can be explained on the basis of non‐covalant interaction like ion−dipole interaction, hydrogen bonding interaction and size selectivity. [ABSTRACT FROM AUTHOR]

The formamidase (FMD) enzyme plays an important role in fungal thriving by releasing a secondary nitrogen source as a product of its activity. In Paracoccidioides species, previous studies have demonstrated the upregulation of this enzyme in a wide range of starvation and infective-like conditions. However, Paracoccidioides lutzii formamidase has not yet been defined as a virulence factor. Here, by employing in vivo infections using an fmd-silenced strain in Galleria mellonella larvae model, we demonstrate the influence of formamidase in P. lutzii's immune stimulation and pathogenicity. The formamidase silencing resulted in improper arrangement of the nodules, poor melanogenesis and decreased fungal burden. Thus, we suggest that formamidase may be a piece composing the process of molecular recognition by Galleria immune cells. Furthermore, formamidase silencing doubled the observed survival rate of the larvae, demonstrating its importance in fungal virulence in vivo. Therefore, our findings indicate that formamidase contributes to Galleria's immune incitement and establishes the role of this enzyme as a P. lutzii virulence factor. Author summary: The study of fungal neglected pathogens is of significant importance for the elucidation of the mechanisms underlying the diseases they cause. The Paracoccidioides lutzii fungus is a pathogen endemic to Latin America, which causes disease in vulnerable portions of society. To cause the disease, the fungal cells must overcome the immune system and obtain nutrients that are typically withdrawn by the host. In this regard, different molecules are crucial for the establishment of infection. The formamidase enzyme plays a role in the survival of the fungus P. lutzii. Our study, presented below, demonstrates that formamidase silencing affects the immune response of G. mellonella larvae to the fungus, resulting in impairment of nodule formation, diminished melanin production, and a reduction in fungal burden. Furthermore, silencing formamidase expression in P. lutzii doubles the survival rate of larvae infected by the fungus, showing its importance for these yeast cells to infect this animals. [ABSTRACT FROM AUTHOR]

The aggregation of amyloid peptides and proteins into toxic oligomers is a hallmark of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Machado‐Joseph's disease, and transmissible spongiform encephalopathies. Inhibition of amyloid oligomers formation and interactions with biological counterparts, as well as the triggering of non‐toxic amorphous aggregates, are strategies towards preventive interventions against these pathologies. NMR spectroscopy addresses the need for structural characterization of amyloid proteins and their aggregates, their binding to inhibitors, and rapid screening of compound libraries for ligand identification. Here we briefly discuss the solution experiments constituting the NMR spectroscopist's toolkit and provide examples of their application. [ABSTRACT FROM AUTHOR]

Cyclic polymers, which are found in the field of biopolymers, exhibit unique physical properties such as suppressed molecular mobility. Considering thermodynamics, the suppressed molecular mobility of cyclic polymers is expected to prevent unfavorable entropy loss in molecular interactions. In this study, we synthesized cyclic glycopolymers carrying galactose units and investigated the effects of their molecular mobility on the interactions with a lectin (peanut agglutinin). The synthesized cyclic glycopolymers exhibited delayed elution time on size exclusion chromatography and a short spin‐spin relaxation time, indicating typical characteristics of cyclic polymers, including smaller hydrodynamic size and suppressed molecular mobility. The hemagglutination inhibition assay revealed that the cyclic glycopolymers exhibited weakened interactions with peanut agglutinin compared to the linear counterparts, attributable to the suppressed molecular mobility. Although the results are contrary to our expectations, the impact of polymer topology on molecular recognition remains intriguing, particularly in the context of protein repellent activity in the biomedical field. [ABSTRACT FROM AUTHOR]

Mycotoxin contamination in foodstuffs and agricultural products has posed a serious hazard to human health and raised international concern. The progress of cost-effective, facile, rapid and reliable analytical tools for mycotoxin determination is in urgent need. In this regard, the potential utility of metal-organic frameworks (MOFs) as a class of crystalline porous materials has sparked immense attention due to their large specific surface area, adjustable pore size, nanoscale framework structure and good chemical stability. The amalgamation of MOFs with high-affinity aptamers has resulted in the progress of advanced aptasensing methods for clinical and food/water safety diagnosis. Aptamers have many advantages over classical approaches as exceptional molecular recognition constituents for versatile bioassays tools. The excellent sensitivity and selectivity of the MOF-aptamer biocomposite nominate them as efficient lab-on-chip tools for portable, label-free, cost-effective and real-time screening of mycotoxins. Current breakthroughs in the concept, progress and biosensing applications of aptamer functionalized MOFs-derived electrochemical and optical sensors for mycotoxins have been discussed in this study. We first highlighted an overview part, which provides some insights into the functionalization mechanisms of MOFs with aptamers, offering a foundation to create MOFs-based aptasensors. Then, we discuss various strategies to design high-performance MOFs-based aptamer scaffolds, which serve as either signal nanoprobe carriers or signal nanoprobes and their applications. We perceived that applications of optical aptamers are in their infancy in comparison with electrochemical MOFs-derived aptasensors. Finally, current challenges and prospective trends of MOFs-aptamer sensors are discussed. [ABSTRACT FROM AUTHOR]

Metallo‐β‐lactamases (MβLs) hydrolyze and inactivate β‐lactam antibiotics, are a pivotal mechanism conferring resistance against bacterial infections. SMB‐1, a novel B3 subclass of MβLs from Serratia marcescens could deactivate almost all β‐lactam antibiotics including ampicillin (AMP), which has posed a serious threat to public health. To illuminate the mechanism of recognition and interaction between SMB‐1 and AMP, various fluorescence spectroscopy techniques and molecular dynamics simulation were employed. The results of quenching spectroscopy unraveled that AMP could make SMB‐1 fluorescence quenching that mechanism was the static quenching; the synchronous and three‐dimensional fluorescence spectra validated that the microenvironment and conformation of SMB‐1 were altered after interaction with AMP. The molecular dynamics results demonstrated that the whole AMP enters the binding pocket of SMB‐1, even though with a relatively bulky R1 side chain. Loop1 and loop2 in SMB‐1 undergo significant fluctuations, and α2 (71–73) and local α5 (186–188) were turned into random coils, promoting zinc ion exposure consistent with circular dichroism spectroscopy results. The binding between them was driven by a combination of enthalpy and entropy changes, which was dominated by electrostatic force in agreement with the fluorescence observations. The present study brings structural insights and solid foundations for the design of new substrates for β‐lactamases and the development of effective antibiotics that are resistant to superbugs. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants. Stat3 can bind to specific DNA response elements and serves as a transcription factor to promote the translation of some invasion/migration-related target genes, considered as a potential anticancer target. Here, molecular docking and molecular dynamics (MD) simulation both were used to explore molecular recognition of quercetin with Stat3. The results show that quercetin impairs DNA transcription efficiency by hindering Stat3 dimerization, partially destroying DNA conformation. Specifically, when the ligand occupies the SH2 cavity of the enzyme, spatial rejection is not conductive to phosphokinase binding. It indirectly prevents the phosphorylation of Y705 and the formation of Stat3 dimer. When the inhibitor binds to the DT1005 position, it obviously shortens the distance between DNA and DBD, enhances their binding capacity, and thereby reduces the degree of freedom required for transcription. This work not only provides the binding modes between Stat3 and quercetin, but also contributes to the optimization and design of such anti-cancer inhibitors. [ABSTRACT FROM AUTHOR]

Accurate and efficient molecular recognition plays a crucial role in the fields of molecular detection and diagnostics. Conventional trial‐and‐error‐based molecular recognition approaches have always been challenged in distinguishing minimal differences between targets and non‐targets, such as single nucleotide polymorphisms (SNPs) of oligonucleotides. To address these challenges, here, a novel concept of dynamic addressing analysis is proposed. In this concept, by dissecting the regions of the target and creating a corresponding recognizer, it is possible to eliminate the inaccuracy and inefficiency of recognition. To achieve this concept, a Dynamic Addressing Molecular Robot (DAMR), a DNA‐based dynamic addressing device is developed which is capable of dynamically locating targets. DAMR is designed to first bind to the conserved region of the target while addressing the specific region dynamically until accurate recognition is achieved. DAMR has provided an approach for analyzing low‐resolution targets and has been used for analyzing SNP of miR‐196a2 in both cell and serum samples, which has opened new avenues for effective and efficient molecular recognition. [ABSTRACT FROM AUTHOR]

Biomarkers play a pivotal role in the screening, diagnosis, prevention, and post-treatment follow-up of various malignant tumors. In certain instances, identifying these markers necessitates prior treatment due to the complex nature of the tumor microenvironment. Consequently, advancing techniques that exhibit selectivity, specificity, and enable streamlined analysis hold significant importance. Molecularly imprinted polymers (MIPs) are considered synthetic antibodies because they possess the property of molecular recognition with high selectivity and sensitivity. In recent years, there has been a notable surge in the investigation of these materials, primarily driven by their remarkable adaptability in terms of tailoring them for specific target molecules and integrating them into diverse analytical technologies. This review presents a comprehensive analysis of molecular imprinting techniques, highlighting their application in developing sensors and analytical methods for cancer detection, diagnosis, and monitoring. Therefore, MIPs offer great potential in oncology and show promise for improving the accuracy of cancer screening and diagnosis procedures. [ABSTRACT FROM AUTHOR]

Plant recognition of pathogen-associated molecular patterns (PAMPs) is pivotal in triggering immune responses, highlighting their potential as inducers of plant immunity. However, the number of PAMPs identified and applied in such contexts remains limited. In this study, we characterize a novel PAMP, designated Ss4368, which is derived from Scleromitrula shiraiana. Ss4368 is specifically distributed among a few fungal genera, including Botrytis, Monilinia, and Botryotinia. The transient expression of Ss4368 elicits cell death in a range of plant species. The signaling peptides, three conserved motifs, and cysteine residues (C46, C88, C112, C130, and C148) within Ss4368 are crucial for inducing robust cell death. Additionally, these signaling peptides are essential for the protein's localization to the apoplast. The cell death induced by Ss4368 and its homologous protein, Bc4368, is independent of the SUPPRESSOR OF BIR1-1 (SOBIR1), BRI1-ASSOCIATED KINASE-1 (BAK1), and salicylic acid (SA) pathways. Furthermore, the immune responses triggered by Ss4368 and Bc4368 significantly enhance the resistance of Nicotiana benthamiana to Phytophthora capsici. Therefore, we propose that Ss4368, as a novel PAMP, holds the potential for developing strategies to enhance plant resistance against P. capsici. [ABSTRACT FROM AUTHOR]

Previous work has shown that binding of target proteins to a sparse, unbiased sample of all possible peptide sequences is sufficient to train a machine learning model that can then predict, with statistically high accuracy, target binding to any possible peptide sequence of similar length. Here, highly sequence-specific molecular recognition is explored by measuring binding of 8 monoclonal antibodies (mAbs) with specific linear cognate epitopes to an array containing 121,715 near-random sequences about 10 residues in length. Network models trained on resulting sequence-binding values are used to predict the binding of each mAb to its cognate sequence and to an in silico generated one million random sequences. The model always ranks the binding of the cognate sequence in the top 100 sequences, and for 6 of the 8 mAbs, the cognate sequence ranks in the top ten. Practically, this approach has potential utility in selecting highly specific mAbs for therapeutics or diagnostics. More fundamentally, this demonstrates that very sparse random sampling of a large amino acid sequence spaces is sufficient to generate comprehensive models predictive of highly specific molecular recognition. Measurements of the binding of eight monoclonal antibodies to an array of 121,715 near-random peptide sequences demonstrates that sparse random sampling can be used to train machine learning models to predict highly specific amino acid sequence recognition. [ABSTRACT FROM AUTHOR]

A water‐soluble prism[5]arene host can form endo‐cavity complexes with hydrophilic organic substances in water by displacing frustrated water molecules from its deep cavity. Water molecules structured at both rims of the prismarene host can mediate hydrogen bonding interactions with the guest. Water‐mediated hydrogen bonding interactions were invoked here to elucidate the elevated binding affinities and selectivity of the prismarene host toward hydrophilic organic guests. We show that water at the interface of a host‐guest complex can act as an extension of the host structure, facilitating the accommodation of neutral guests within the binding site. This study highlights the crucial role of water in facilitating supramolecular interactions between a deep‐cavity prismarene host and organic hydrophilic guests in aqueous medium. [ABSTRACT FROM AUTHOR]

Single‐walled carbon nanotubes (SWCNTs) are desirable nanoparticles for sensing biological analytes due to their photostability and intrinsic near‐infrared fluorescence. Previous strategies for generating SWCNT nanosensors have leveraged nonspecific adsorption of sensing modalities to the hydrophobic SWCNT surface that often require engineering new molecular recognition elements. An attractive alternate strategy is to leverage pre‐existing molecular recognition of proteins for analyte specificity, yet attaching proteins to SWCNT for nanosensor generation remains challenging. Toward this end, a generalizable platform is introduced to generate protein‐SWCNT‐based optical sensors and use this strategy to synthesize a hydrogen peroxide (H2O2) nanosensor by covalently attaching horseradish peroxidase (HRP) to the SWCNT surface. A concentration‐dependent response is demonstrated to H2O2, confirming the nanosensor can image H2O2 in real‐time, and assess the nanosensor's selectivity for H2O2 against a panel of biologically relevant analytes. Taken together, these results demonstrate successful covalent attachment of enzymes to SWCNTs while preserving both intrinsic SWCNT fluorescence and enzyme function. It is anticipated this platform can be adapted to covalently attach other proteins of interest including other enzymes for sensing or antibodies for targeted imaging and cargo delivery. [ABSTRACT FROM AUTHOR]

Single wall carbon nanotubes (SWCNTs) functionalized with (bio-)polymers such as DNA are soluble in water and sense analytes by analyte-specific changes of their intrinsic fluorescence. Such SWCNT-based (bio-)sensors translate the binding of a molecule (molecular recognition) into a measurable optical signal. This signal transduction is crucial for all types of molecular sensors to achieve high sensitivities. Although there is an increasing number of SWCNT-based sensors, there is yet no molecular understanding of the observed changes in the SWCNT's fluorescence. Here, we report THz experiments that map changes in the local hydration of the solvated SWCNT upon binding of analytes such as the neurotransmitter dopamine or the vitamin riboflavin. The THz amplitude signal serves as a measure of the coupling of charge fluctuations in the SWCNTs to the charge density fluctuations in the hydration layer. We find a linear (inverse) correlation between changes in THz amplitude and the intensity of the change in fluorescence induced by the analytes. Simulations show that the organic corona shapes the local water, which determines the exciton dynamics. Thus, THz signals are a quantitative predictor for signal transduction strength and can be used as a guiding chemical design principle for optimizing fluorescent biosensors. SWCNTs are pivotal optical molecular sensors, but until now, the underlying mechanism how the binding of analytes affects the fluorescence remained elusive. This study has elucidated that coupling between exciton-coupled plasmon modes of SWCNTs and THz water modes is a significant factor. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) are pivotal in modulating protein functions and influencing cellular processes like signaling, localization, and degradation. The complexity of these biological interactions necessitates efficient predictive methodologies. In this work, we introduce PTMGPT2, an interpretable protein language model that utilizes prompt-based fine-tuning to improve its accuracy in precisely predicting PTMs. Drawing inspiration from recent advancements in GPT-based architectures, PTMGPT2 adopts unsupervised learning to identify PTMs. It utilizes a custom prompt to guide the model through the subtle linguistic patterns encoded in amino acid sequences, generating tokens indicative of PTM sites. To provide interpretability, we visualize attention profiles from the model's final decoder layer to elucidate sequence motifs essential for molecular recognition and analyze the effects of mutations at or near PTM sites to offer deeper insights into protein functionality. Comparative assessments reveal that PTMGPT2 outperforms existing methods across 19 PTM types, underscoring its potential in identifying disease associations and drug targets. PTMGPT2, which leverages prompt-based fine-tuning on protein sequences, predicts post-translational modifications (PTMs) with higher accuracy. It interprets attention scores as motifs and identifies pathogenic mutations, providing insights into protein functionality. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Biological cells exhibit diverse phenomena induced through linking of chemical reactions of molecules and solid surface contact. It is then a significant topic in the field of chemistry to study phenomena induced through this linking using synthetic systems, which can promote our understanding of biological phenomena and can be applied to the development of novel functions. Silica nanoparticles (SNPs), which are synthetic inorganic materials, are attractive for such purposes, because of their following characteristics: they can adsorb large amounts of molecules on their surfaces, they can aggregate through contact between SNPs as well as contact between molecules and SNPs, and the molecules can be easily removed from solutions by precipitation. The contact of SNP surfaces with molecules then affects chemical reactions of molecules and also behaviors of SNPs. This article describes systems derived from synthetic helical molecules and SNPs, which exhibit notable phenomena including selective adsorption and molecular recognition, equilibrium shift, step kinetics with induction period, precipitation with flow and sweeping, and disaggregation and desorption by sonication, in which the high affinity of helical molecules with SNP surfaces plays important roles. Mechanistic models that explain the phenomena are provided. Possible applications are also discussed, including the separation of molecules, capture of intermediates, the storage and release of molecules, equilibrium shift, clocking, and the translation of mechanical stimulations into chemical reactions. Key Scientists: [ABSTRACT FROM AUTHOR]

Lectins are sugar interacting proteins which bind specific glycans reversibly and have ubiquitous presence in all forms of life. They have diverse biological functions such as cell signaling, molecular recognition, etc. C-type lectins (CTL) are a group of proteins from the lectin family which have been studied extensively in animals and are reported to be involved in immune functions, carcinogenesis, cell signaling, etc. The carbohydrate recognition domain (CRD) in CTL has a highly variable protein sequence and proteins carrying this domain are also referred to as C-type lectin domain containing proteins (CTLD). Because of this low sequence homology, identification of CTLD from hypothetical proteins in the sequenced genomes using homology based programs has limitations. Machine learning (ML) tools use characteristic features to identify homologous sequences and it has been used to develop a tool for identification of CTLD. Initially 500 sequences of well annotated CTLD and 500 sequences of non CTLD were used in developing the machine learning model. The classifier program Linear SVC from sci kit library of python was used and characteristic features in CTLD sequences like dipeptide and tripeptide composition were used as training attributes in various classifiers. A precision, recall and multiple correlation coefficient (MCC) value of 0.92, 0.91 and 0.82 respectively were obtained when tested on external test set. On fine tuning of the parameters like kernel, C value, gamma, degree and increasing number of non CTLD sequences there was improvement in precision, recall and MCC and the corresponding values were 0.99, 0.99 and 0.96. New CTLD have also been identified in the hypothetical segment of human genome using the trained model. The tool is available on our local server for interested users. [ABSTRACT FROM AUTHOR]

The world is transitioning into an aging society, a phenomenon that escalates the risk of age‐related diseases, posing a significant threat to human health. Addressing how to delay aging or achieve healthy aging has become an urgent and pivotal issue. Presently, diverse anti‐aging drugs are under development and entering clinical validation stages. However, the absence of specific aging biomarkers has hindered the identification of corresponding targets for diagnosing and treating aging and age‐related diseases. Aptamer, a novel molecular recognition tool, has found broad application in diagnosing and treating various diseases. Additionally, cell‐based selection holds the potential to identify unidentified molecules that could serve as biomarkers for diseases. Recent years have seen a surge in attention towards aging and age‐related diseases, with the application of aptamer in this domain rapidly advancing. Consequently, this review will provide a concise overview of the aging, with a focus on the utilisation of aptamer in aging and age‐related diseases. [ABSTRACT FROM AUTHOR]

Tick Anticoagulant Peptide (TAP), a 60-amino acid protein from the soft tick Ornithodoros moubata, inhibits activated coagulation factor X (fXa) with almost absolute specificity. Despite TAP and Bovine Pancreatic Trypsin Inhibitor (BPTI) (i.e., the prototype of the Kunitz-type protease inhibitors) sharing a similar 3D fold and disulphide bond topology, they have remarkably different amino acid sequence (only ~24% sequence identity), thermal stability, folding pathways, protease specificity, and even mechanism of protease inhibition. Here, fully active and correctly folded TAP was produced in reasonably high yields (~20%) by solid-phase peptide chemical synthesis and thoroughly characterised with respect to its chemical identity, disulphide pairing, folding kinetics, conformational dynamics, and fXa inhibition. The versatility of the chemical synthesis was exploited to perform structure–activity relationship studies on TAP by incorporating non-coded amino acids at positions 1 and 3 of the inhibitor. Using Hydrogen–Deuterium Exchange Mass Spectrometry, we found that TAP has a remarkably higher conformational flexibility compared to BPTI, and propose that these different dynamics could impact the different folding pathway and inhibition mechanisms of TAP and BPTI. Hence, the TAP/BPTI pair represents a nice example of divergent evolution, while the relative facility of TAP synthesis could represent a good starting point to design novel synthetic analogues with improved pharmacological profiles. [ABSTRACT FROM AUTHOR]

The Gal(α1‐3)Gal is the terminal disaccharide unit of the α‐Gal epitope [Gal(α1‐3)Gal(β1‐4)GlcNAc], an exogenous antigenic determinant with several clinical implications, found in all non‐primate mammals and in several dangerous pathogens, including certain protozoa and mycobacteria. Its absence in humans makes the α‐Gal epitope an interesting target for several infectious diseases. Here we present the development of a macrocyclic tweezers‐shaped receptor, resulting from the combination of the structural features of two predecessors belonging to the family of diaminocarbazole receptors, which exhibits binding properties in the low millimolar range toward the Gal(α1‐3)Gal disaccharide of the α‐Gal antigen. [ABSTRACT FROM AUTHOR]

Porphyrin atropisomerism, which arises from restricted σ‐bond rotation between the macrocycle and a sufficiently bulky substituent, was identified in 1969 by Gottwald and Ullman in 5,10,15,20‐tetrakis(o‐hydroxyphenyl)porphyrins. Henceforth, an entirely new field has emerged utilizing this transformative tool. This review strives to explain the consequences of atropisomerism in porphyrins, the methods which have been developed for their separation and analysis and present the diverse array of applications. Porphyrins alone possess intriguing properties and a structure which can be easily decorated and molded for a specific function. Therefore, atropisomerism serves as a transformative tool, making it possible to obtain even a specific molecular shape. Atropisomerism has been thoroughly exploited in catalysis and molecular recognition yet presents both challenges and opportunities in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Circularly polarized luminescence (CPL) materials have been widely used in the fields of bioimaging, optoelectronic devices, and optical communications. The supramolecular interaction, involving harnessing non-covalent interactions between host and guest molecules to control their arrangements and assemblies, represents an advanced approach for facilitating the development of CPL materials and finely constructing and tuning the desired CPL properties. Cyclodextrins (CDs) are cyclic natural polysaccharides, which have also been ubiquitous in various fields such as molecular recognition, drug encapsulation, and catalyst separation. By adjusting the interactions between CDs and guest molecules precisely, composite materials with CPL properties can be facilely generated. This review aims to outline the design strategies and performance of CD-based CPL materials comprehensively and provides a detailed illustration of the interactions between host and guest molecules. [ABSTRACT FROM AUTHOR]

We present a novel solid form of monascin, an azaphilonoid derivative extracted from Monascus purpureus‐fermented rice. The crystal structure, C21H26O5, was characterized by single‐crystal X‐ray diffraction and belongs to the orthorhombic space group P212121. To gain insight into the electronic properties of the short contacts in the crystalline state of monascin, we utilized the Experimental Library of Multipolar Atom Model 2 (ELMAM2) database to transfer the electron density of monascin in its crystalline state. Hirshfeld surface analysis, fingerprint analysis, electronic properties and energetic characterization reveal that intermolecular C—H...O hydrogen bonds play a crucial role in the noncovalent bonding interactions by connecting molecules into two‐ and three‐dimensional networks. The molecular electrostatic potential (MEP) map of the monascin molecule demonstrates that negatively charged regions located at four O atoms are favoured binding sites for more positively charged amino acid residues during molecular recognition. In addition, powder X‐ray diffraction confirms that no transformation occurs during the crystallization of monascin. [ABSTRACT FROM AUTHOR]

Aiming to endow natural minerals with fast, high-sensitivity, and controllable smart light, humidity, solvent and temperature responsiveness, a novel ceramic clay and cucurbituril (CB) guest-host system (MVCB) inspired by nature was self-assembled and rearranged via an ingenious and simple design successfully. For the first time, the multi-functional MVCB not only displayed a high intelligent multi-stimuli responsiveness as light, humidity, solvent, and temperature switches, but also had multiple selective molecular recognition responses because of different organic vapor with CB and asymmetrical bilayer clay. For instance, due to the factors of guest-host and slow release, the average response speed of self-assembled shuffling the MVCB in methanol was as high as 108°/s compared with bilayer film without CB (20°/s). Besides, the MVCB exhibited controllable swift movement and was bending for grabbing three times its own weight. Moreover, the ultra-wide operating temperature of the MVCB from was ranging −196 to 300 °C under extreme condition. More interestingly, the MVCB presented a unique and compliable self-driven, smart switch, shape memory, environmental awareness and soft robotic gripper owing to the asymmetrical swelling and supramolecular of the CB. This work not only brings a simple, cost-effective, large-scale, and efficient strategy for multi-functionalized natural minerals materials, but also opens potential applications for intelligent response, extremely resistant substances, energy conversion and soft robotics. [ABSTRACT FROM AUTHOR]

Introduction: The design of carbohydrate-binding agents (artificial carbohydrate receptors) that enable selective and effective biomimetic recognition via noncovalent interactions is aimed either at a better understanding of natural recognition phenomena or at various potential applications in medicine and other fields. Although very interesting artificial receptors have been developed, the exact prediction of the receptor selectivity remains a challenge. Results and Methods: A molecular architecture based on a 1,3,5-substituted 2,4,6-triethylbenzene backbone bearing two aminopyridine- or aminopyrimidine-based recognition units and a purine moiety, which acts as both a hydrogen bonding site and a bridging component for the incorporation of additional substituents, has proved to be very useful for the development of effective carbohydrate-binding agents. This type of compounds has the ability to bind suitable carbohydrates through combined noncovalent interactions, where CH···π interactions can be formed on both faces of the carbohydrate substrate. The successful syntheses of the target compounds can be realized by the use of microwave irradiation and sealed tubes. The performed binding studies included ¹ H NMR spectroscopic titrations and measurements by isothermal titration calorimetry. Conclusion: The new compounds were developed as artificial receptors especially for carbohydrates with an all-equatorial substitution pattern and have the ability to predictably form strong 1:1 complexes with a suitable substrate. The use of the purine moiety in the construction of carbohydrate receptors with a 1,3,5-substituted 2,4,6-triethylbenzene backbone has proved to be a very promising approach. The possibilities for structural variation of this molecular architecture are manifold. As a result, a wide range of compounds can be synthesized to perform extensive studies on the relationships between structure and binding efficiency [ABSTRACT FROM AUTHOR]

Flexible, water-soluble hosts are capable of selective molecular recognition in cellular environments and can detect neurotransmitters such as choline in cells. Both cationic and anionic water-soluble self-folded deep cavitands can recognize suitable styrylpyridinium dyes in cellular interiors. The dyes selectively accumulate in nucleotide-rich regions of the cell nucleus and cytoplasm. The hosts bind the dyes and promote their relocation to the outer cell membrane: the lipophilic cavitands predominantly reside in membrane environments but are still capable of binding suitable targets in other cellular organelles. Incubating the cells with structurally similar biomarkers such as choline, cholamine, betaine, or butyrylcholine illustrates the selective recognition. Choline and butyrylcholine can be bound by the hosts, but minimal binding is seen with betaine or cholamine. Varying the dye allows control of the optical detection method, and both "turn-on" sensing and "turn-off" sensing are possible.

Abstract The pH‐dependent assembly of Toll‐like receptors (TLRs), which triggers a threshold‐like response, is a key principle in immune signaling. While crystallography has revealed the intricate structure of these assembly complexes, the mechanisms underlying their pH dependency remain unclear. Herein, constant pH simulations and metadynamics are employed to investigate the pH‐dependent assembly and stability of the TLR3/dsRNA signaling complex. The findings demonstrate that system pH regulates complex assembly and stability by modulating the protonation and charge states of histidines. Histidines in TLR3 act as pH‐dependent, positively charged binding sites that capture negatively charged dsRNA. Additionally, these histidines form a [H682⁺]—[E626⁻] dipole, facilitating the assembly of two TLR3 molecules into an antisymmetric dimer through dipole–dipole interactions. Surprisingly, TLR3 can shift the pKa values of key histidines from their model pKa of 6.5, increasing protonation likelihood and enhancing ligand binding. Notably, the aromatic residue Phe84, located within the dsRNA binding site [His39⁺–His60⁺–Phe84–His108⁺], alters the pKa of His60 through cation‐π interactions with its protonated state. This study offers new insights into the molecular mechanisms underlying pH‐dependent immune signaling via higher‐order assemblies and suggests potential applications for histidine in self‐assembling biomaterials.

Oligonucleotide drugs, an emerging modulator class, hold promise for targeting previously undruggable biomacromolecules. To date, only 18 oligonucleotide drugs, including sought-after antisense oligonucleotides (ASOs) and splice-switching oligonucleotides, have approval from the U.S. Food and Drug Administration. These agents effectively bind mRNA, inducing degradation or modulating splicing. Current oligonucleotide drug design strategies prioritize full Watson-Crick base pair (bp) complementarity, overlooking mRNA target three-dimensional shapes. Given that mRNA conformational diversity can impact hybridization, incorporating mRNA key structural properties into the design may expedite ASO lead discovery. Using atomistic molecular dynamics simulations inspired by experimental data, we demonstrate the advantages of incorporating common triple bps into the design of ASOs targeting RNA hairpin motifs, which are highly accessible regions for interactions. By using an RNA pseudoknot modified into an ASO-hairpin complex, we investigate the effects of ASO length and hairpin loop mutations. Our findings suggest that ASO-mRNA complex stability is influenced by ASO length, number of common triple bps, and the dynamic accessibility of bases in the hairpin loop. Our study offers new mechanistic insights into ASO-mRNA complexation and underscores the value of pseudoknots in constructing training datasets for machine learning models aimed at designing novel ASO leads.

"Chemistry - A European Journal Turns 30" reflects on the history and evolution of the journal since its launch in 1995. The journal has been a cornerstone of Chemistry Europe, covering diverse topics in chemistry over the years. In its 30th year, Chemistry - A European Journal remains committed to excellence, innovation, and representing modern chemistry, with plans to celebrate its anniversary with a symposium in Strasbourg. [Extracted from the article]

Carbonic anhydrase (CA) was among the first proteins whose X-ray crystal structure was solved to atomic resolution. CA proteins have essentially the same fold and similar active centers that differ in only several amino acids. Primary sulfonamides are well defined, strong and specific binders of CA. However, minor variations in chemical structure can significantly alter their binding properties. Over 1000 sulfonamides have been designed, synthesized and evaluated to understand the correlations between the structure and thermodynamics of their binding to the human CA isozyme family. Compound binding was determined by several binding assays: fluorescence-based thermal shift assay, stopped-flow enzyme activity inhibition assay, isothermal titration calorimetry and competition assay for enzyme expressed on cancer cell surfaces. All assays have advantages and limitations but are necessary for deeper characterization of these protein–ligand interactions. Here, the concept and importance of intrinsic binding thermodynamics is emphasized and the role of structure–thermodynamics correlations for the novel inhibitors of CA IX is discussed – an isozyme that is overexpressed in solid hypoxic tumors, and thus these inhibitors may serve as anticancer drugs. The abundant structural and thermodynamic data are assembled into the Protein–Ligand Binding Database to understand general protein–ligand recognition principles that could be used in drug discovery.

Appending functional groups to the exterior of Zn4 L4 self-assembled cages allows gated control of anion binding. While the unfunctionalized cages contain aryl groups in the ligand that can freely rotate, attaching inert functional groups creates a "doorstop", preventing rotation and slowing the guest exchange rate, even though the interiors of the host cavities are identically structured. The effects on anion exchange are subtle and depend on multiple factors, including anion size, the nature of the leaving anion, and the electron-withdrawing ability and steric bulk of the pendant groups. Multiple exchange mechanisms occur, and the nature of the external groups controls associative and dissociative exchange processes: these bulky groups affect both anion egress and ingress, introducing an extra layer of selectivity to the exchange. Small changes can have large effects: affinities for anions as similar as PF6 - and SbF6 - can vary by as much as 400-fold between identically sized cavities.

The accumulation of organic micropollutants (OMP) in aquatic systems is a major societal problem that can be addressed by approaches including nanofiltration, flocculation, reverse osmosis and adsorptive methods using insoluble materials (e.g. activated carbon, MOFs, nanocomposites). More recently, polymeric versions of supramolecular hosts (e.g. cyclodextrins, calixarenes, pillararenes) have been investigated as OMP sequestrants. Herein, we report our study of the use of water insoluble dimethylcatechol walled acyclic cucurbit[n]uril (CB[n]) hosts as solid state sequestrants for a panel of five OMPs. A series of hosts (H1–H4) were synthesized by reaction of glycoluril oligomer (monomer–tetramer) with 3,6‐dimethylcatechol and fully characterized by spectroscopic means and x‐ray crystallography. The solid hosts sequester OMPs from water with removal efficiencies exceeding 90 % in some cases. The removal efficiencies of the new hosts parallel the known molecular recognition properties of analogous water soluble acyclic CB[n]. OMP uptake by solid host occurs rapidly (≈120 seconds). Head‐to‐head comparison with CB[6] in batch‐mode separation and DARCO activated carbon in flow‐through separation mode show that tetramer derived host (H4) performs very well under identical conditions. The work establishes insoluble acyclic CB[n]‐type receptors as a promising new platform for OMP sequestration. [ABSTRACT FROM AUTHOR]

Bacterial synthesis of vitamin B2 generates a by‐product, 5‐(2‐oxopropylideneamino)‐d‐ribityl‐aminouracil (5‐OP‐RU), with potent immunological properties in mammals, but it is rapidly degraded in water. This natural product covalently bonds to the key immunological protein MR1 in the endoplasmic reticulum of antigen presenting cells (APCs), enabling MR1 refolding and trafficking to the cell surface, where it interacts with T cell receptors (TCRs) on mucosal associated invariant T lymphocytes (MAIT cells), activating their immunological and antimicrobial properties. Here, we strategically modify this natural product to understand the molecular basis of its recognition by MR1. This culminated in the discovery of new water‐stable compounds with extremely powerful and distinctive immunological functions. We report their capacity to bind MR1 inside APCs, triggering its expression on the cell surface (EC50 17 nM), and their potent activation (EC50 56 pM) or inhibition (IC50 80 nM) of interacting MAIT cells. We further derivatize compounds with diazirine‐alkyne, biotin, or fluorophore (Cy5 or AF647) labels for detecting, monitoring, and studying cellular MR1. Computer modeling casts new light on the molecular mechanism of activation, revealing that potent activators are first captured in a tyrosine‐ and serine‐lined cleft in MR1 via specific pi‐interactions and H‐bonds, before more tightly attaching via a covalent bond to Lys43 in MR1. This chemical study advances our molecular understanding of how bacterial metabolites are captured by MR1, influence cell surface expression of MR1, interact with T cells to induce immunity, and offers novel clues for developing new vaccine adjuvants, immunotherapeutics, and anticancer drugs. [ABSTRACT FROM AUTHOR]

In recent years, European Union member states have hastened energy policy deliberations to address supply and sustainability concerns, placing a significant emphasis on nuclear energy as a means to achieve decarbonization goals. However, despite its significant role in power generation, nuclear energy faces significant challenges linked to fuel reprocessing and waste disposal, that hinder its broader expansion. In this context, the separation of technetium represents a concerning issue. Indeed, technetium's catalytic activity can impede the extraction of uranium, neptunium, and plutonium, affecting waste reprocessing efficiency. Additionally, the stable form of technetium in aerobic conditions, pertechnetate (TcO4−), poses risks of groundwater contamination due to its mobility and solubility. Hence, sensing and separation of TcO4− is imperative for both nuclear fuel processing and minimising radioactive contamination in the environment. However, the binding of TcO4− and its separation from contaminated solutions present challenges due to the acidic (or basic) waste components and the high ionic strength in real matrices. Supramolecular chemists have addressed these issues by designing receptors inspired by molecular recognition principles. This article explores recent advancements and future directions in TcO4− sensing and separation (using extraction and sorption) with a focus on molecular hosts. Metal‐organic receptors will also be discussed. [ABSTRACT FROM AUTHOR]

In recent years, European Union member states have hastened energy policy deliberations to address supply and sustainability concerns, placing a significant emphasis on nuclear energy as a means to achieve decarbonization goals. However, despite its significant role in power generation, nuclear energy faces significant challenges linked to fuel reprocessing and waste disposal, that hinder its broader expansion. In this context, the separation of technetium represents a concerning issue. Indeed, technetium's catalytic activity can impede the extraction of uranium, neptunium, and plutonium, affecting waste reprocessing efficiency. Additionally, the stable form of technetium in aerobic conditions, pertechnetate (TcO4−), poses risks of groundwater contamination due to its mobility and solubility. Hence, sensing and separation of TcO4− is imperative for both nuclear fuel processing and minimising radioactive contamination in the environment. However, the binding of TcO4− and its separation from contaminated solutions present challenges due to the acidic (or basic) waste components and the high ionic strength in real matrices. Supramolecular chemists have addressed these issues by designing receptors inspired by molecular recognition principles. This article explores recent advancements and future directions in TcO4− sensing and separation (using extraction and sorption) with a focus on molecular hosts. Metal‐organic receptors will also be discussed. [ABSTRACT FROM AUTHOR]

Achieving ligand subtype selectivity within highly homologous subtypes of G-protein-coupled receptor (GPCR) is critical yet challenging for GPCR drug discovery, primarily due to the unclear mechanism underlying ligand subtype selectivity, which hampers the rational design of subtype-selective ligands. Herein, we disclose an unusual molecular mechanism of entropy-driven ligand recognition in cannabinoid (CB) receptor subtypes, revealed through atomic-level molecular dynamics simulations, cryoelectron microscopy structure, and mutagenesis experiments. This mechanism is attributed to the distinct conformational dynamics of the receptor's orthosteric pocket, leading to variations in ligand binding entropy and consequently, differential binding affinities, which culminate in specific ligand recognition. We experimentally validated this mechanism and leveraged it to design ligands with enhanced or ablated subtype selectivity. One such ligand demonstrated favorable pharmacokinetic properties and significant efficacy in rodent inflammatory analgesic models. More importantly, it is precisely due to the high subtype selectivity obtained based on this mechanism that this ligand does not show addictive properties in animal models. Our findings elucidate the unconventional role of entropy in CB receptor subtype selectivity and suggest a strategy for rational design of ligands to achieve entropy-driven subtype selectivity for many pharmaceutically important GPCRs. [ABSTRACT FROM AUTHOR]

Natural membrane receptors are proteins that can report on changes in the concentration of external chemical messengers. Messenger binding to a receptor produces conformational changes that are relayed through the membrane into the cell; this information allows cells to adapt to changes in their environment. Artificial membrane receptors (R)‐1 and (S)‐1 are helical α‐aminoisobutyric acid (Aib) foldamers that replicate key parts of this information relay. Solution‐phase 19F NMR spectroscopy of zinc(II)‐capped receptor 1, either in organic solvent or in membrane‐mimetic micelles, showed messenger binding produced an enrichment of either left‐ or right‐handed screw‐sense; the chirality of the bound messenger was relayed to the other receptor terminus. Furthermore, in situ production of a chemical messenger in the external aqueous environment could be detected in real‐time by a racemic mixture of receptor 1 in micelles. The hydrolysis of insoluble anhydrides produced carboxylate in the aqueous phase, which bound to the receptors and gave a distinct 19F NMR output from inside the hydrophobic region of the micelles. [ABSTRACT FROM AUTHOR]

The oxime functional group is pivotal in chemistry, finding extensive applications in medical science, catalysis, organic functional group transformations, and the recognition of essential and toxic analytes. While the coordination chemistry of oxime derivatives has been thoroughly explored and several reviews have been published on this topic in reputable journals, a comprehensive review encompassing various aspects such as crystal engineering, cation and anion recognition, as well as coordination chemistry activities, is still in demand. This feature article highlights the diverse applications of oxime derivatives across multiple domains of chemistry, including medicine, agriculture, crystal engineering, coordination chemistry, and molecular recognition studies. Each of the oxime derivatives in this feature article are meticulously described in terms of their medicinal applications, crop protection, crystal engineering attributes, analyte recognition capabilities, and coordination chemistry aspects. By providing a comprehensive overview of their versatile applications, this article aims to inspire researchers to explore and develop novel oxime-based derivatives for future applications. [ABSTRACT FROM AUTHOR]

Emerging infectious diseases, cancer, and other diseases are quickly tested mainly via immune reactions based on specific molecular recognition between antigens and antibodies. By changing the diameter of solid-state pores, biomolecules of various sizes can be rapidly detected at the single-molecule level. The combination of immunoreactions and solid-state pores paves the way for an efficient testing method with high specificity and sensitivity. The challenge in developing this method is achieving quantitative analysis using solid-state pores. Here, we demonstrate a method with a low limit of detection for testing tumor markers using a combination of immunoreactions and solid-state pore technology. Quantitative analysis of the mixing ratio of two and three beads with different diameters was achieved with an error rate of up to 4.7%. The hybrid solid-state pore and immunoreaction methods with prostate-specific antigen (PSA) and anti-PSA antibody-modified beads achieved a detection limit of 24.9 fM PSA in 30 min. The hybrid solid-state pore and immunoreaction enabled the rapid development of easy-to-use tests with lower limit of detection and greater throughput than commercially available immunoassay for point-of-care testing. [ABSTRACT FROM AUTHOR]

Supramolecules are considered as promising materials for volatile organic compounds (VOCs) sensing applications. The proper understanding of the sorption process taking place in host-guest interactions is critical in improving the pattern recognition of supramolecules-based sensing arrays. Here, we report a novel approach to investigate the dynamic host-guest recognition process by employing a bulk acoustic wave (BAW) resonator capable of producing multiple oscillation amplitudes and simultaneously recording multiple responses to VOCs. Self-assembled monolayers (SAMs) of β-cyclodextrin (β-CD) were modified on four BAW sensors to demonstrate the gas-surface interactions regarding oscillation amplitude and SAM length. Based on the method, a virtual sensor array (VSA) type electronic nose (e-nose) can be realized by pattern recognition of multiple responses at different oscillation amplitudes of a single sensor. VOCs analysis was realized respectively by using principal component analysis (PCA) for individual VOC identification and linear discriminant analysis (LDA) for VOCs mixtures classification. [ABSTRACT FROM AUTHOR]

Nucleic acid aptamers are oligonucleotide chains with molecular recognition properties. Compared with antibodies, aptamers show advantages given that they are readily produced via chemical synthesis and elicit minimal immunogenicity in biomedicine applications. Notably, aptamer-encoded nucleic acid assemblies further improve the binding affinity of aptamers with the targets due to their multivalent synergistic interactions. Specially, aptamers can be engineered with special topological arrangements in nucleic acid assemblies, which demonstrate spatial and valence matching towards antigens on viruses, thus showing potential in the detection and therapeutic applications of viruses. This review presents the recent progress on the aptamers explored for SARS-CoV-2 detection and infection treatment, wherein applications of aptamer-based assembly systems are introduced in detail. Screening methods and chemical modification strategies for aptamers are comprehensively summarized, and the types of aptamers employed against different target domains of SARS-CoV-2 are illustrated. The evolution of aptamer-based assembly systems for the detection and neutralization of SARS-CoV-2, as well as the construction principle and characteristics of aptamer-based DNA assemblies are demonstrated. The typically representative works are presented to demonstrate how to assemble aptamers rationally and elaborately for specific applications in SARS-CoV-2 diagnosis and neutralization. Finally, we provide deep insights into the current challenges and future perspectives towards aptamer-based nucleic acid assemblies for virus detection and neutralization in nanomedicine. [ABSTRACT FROM AUTHOR]

Proteins are an eminently important class of ubiquitous biomacromolecules with diverse biological functions, and numerous techniques for their detection, quantification, and localisation have been developed. Many of these methods exploit the selectivity arising from molecular recognition of proteins/antigens by immunoglobulins. The combination of surface-enhanced Raman scattering (SERS) with such "immuno"-techniques to immuno-SERS (iSERS) is the central topic of this review, which is focused on colloidal SERS nanotags, i.e., molecularly functionalised noble metal nanoparticles conjugated to antibodies, for their use in protein assays and ex vivo imaging. After contrasting the fundamental differences between label-free SERS and iSERS, including a balanced description of the advantages and drawbacks of the latter, we describe the usual workflow of iSERS experiments. Milestones in the development of the iSERS technology are summarised from a historical perspective. By highlighting selected examples from the literature, we illustrate the conceptual progress that has been achieved in the fields of iSERS-based protein assays and ex vivo imaging. Finally, we attempt to predict what is necessary to fully exploit the transformative potential of the iSERS technology by stimulating the transition from research in academic labs into applications for the benefit of our society. [ABSTRACT FROM AUTHOR]

Upon pathogenic stimulation, activated neutrophils release nuclear DNA into the extracellular environment, forming web‐like DNA structures known as neutrophil extracellular traps (NETs), which capture and kill bacteria, fungi, and cancer cells. This phenomenon is commonly referred to as NETosis. Inspired by this, we introduce a cell surface‐constrained web‐like framework nucleic acids traps (FNATs) with programmable extracellular recognition capability and cellular behavior modulation. This approach facilitates dynamic key chemical signaling molecule recognition such as adenosine triphosphate (ATP), which is elevated in the extracellular microenvironment, and triggers FNA self‐assembly. This, in turn, leads to in situ tightly interwoven FNAs formation on the cell surface, thereby inhibiting target cell migration. Furthermore, it activates a photosensitizer‐capturing switch, chlorin e6 (Ce6), and induces cell self‐destruction. This cascade platform provides new potential tools for visualizing dynamic extracellular activities and manipulating cellular behaviors using programmable in situ self‐assembling DNA molecular devices. [ABSTRACT FROM AUTHOR]

Despite considerable progress has been made in the understanding of the genetics and molecular biology of renal cell carcinoma (RCC), therapeutic options of patients with papillary renal cell carcinoma (PRCC) are limited. Immunotherapy based on immune checkpoint inhibitors (ICIs) has become a hot point in researching new drug for tumor and been tested in a number of human clinical trials. In this study, an immune-related gene prognostic index (IRGPI) was developed and provided a comprehensive and systematic analysis of distinct phenotypic and molecular portraits in the recognition, surveillance, and prognosis of PRCC. The reliability of the IRGPI was evaluated using independent datasets from GEO database and the expression levels of the genes in the IRGPI detected by real-time PCR. Collectively, the currently established IRGPI could be used as a potential biomarker to evaluate the response and efficacy of immunotherapy in PRCC. [ABSTRACT FROM AUTHOR]

The drug fenoprofen (FN) is available in two forms, R‐ and S‐enantiomers, which need to be separated for optimal therapeutic use. A novel poly(acrylonitrile‐co‐divinylbenzene) (PNB)‐based polymer sorbent designed specifically for S‐fenoprofen (S‐FN) enantioseparation was synthesized. This process began with creating low cross‐linked PNB microparticles through suspension polymerization. Next, hydrazine was introduced to react with the prevalent nitrile groups. The produced cationic hydrazidine‐functionalized polymer particles (HYD‐P) were then combined with anionic S‐FN. The imprinting of S‐FN was achieved by further cross‐linking with glutaraldehyde, which interacted with the NH2 groups. Subsequent acidic elution released the S‐FN enantiomers, leaving behind their specific receptor‐like cavities in the imprinted polymer particles (S‐FN‐P). The properties of the resulting polymers were analyzed using Fourier‐transform infrared (FTIR), 13C NMR, and x‐ray diffraction. Scanning electron microscopy was used to examine the surface structures of the sorbents. Under optimal conditions at pH 7, the sorbent showed an adsorption capacity of 240 mg/g for S‐FN. The chiral separation of the FN racemate achieved high enantiomeric excess (ee) levels, with 96% for R‐FN during loading and 94% for S‐FN during recovery. [ABSTRACT FROM AUTHOR]