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Receptors are lipid bilayer‐resident molecules that perform a myriad of functions in a cell, from recognition to signaling and solute internalization, and are typically based on proteins. Herein, artificial receptors are engineered based on small organic molecules, toward chemical, non‐genetic engineering of cells. Specifically, artificial internalizing receptors are designed for selective targeting and cell‐specific drug delivery. The artificial receptors are shown to afford nanomolar potency of action for the cognate antibody‐drug conjugates. In the chemically engineered cells, the conjugate activity is at the same time more potent and significantly faster than that observed with the use of the pristine drug. In a mixed cell population, an antibody‐drug conjugate targeted to the artificial receptor can selectively eliminate the chemical receptor‐engineered cells. Taken together, these results illustrate that artificial receptors based on small organic molecules are simple by structure but can mediate one of the foundational cellular functions, namely endocytosis, with excellence. Most importantly, these receptors are truly bio‐orthogonal and thus afford a dedicated route of communication with the chemically engineered cells. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have emerged as promising diagnostic biomarkers and therapeutic targets in various diseases. However, there is currently a lack of molecular strategies that can effectively use disease‐associated extracellular miRNAs as input signals to drive therapeutic functions. Herein, we present a modular and programmable miRNA‐responsive chimeric DNA receptor (miRNA‐CDR) capable of biomarker‐driven therapy. By grafting a miRNA‐responsive DNA nanodevice on a natural membrane receptor via aptamer anchoring, miRNA‐CDR can sense extracellular miRNA levels and autonomously induce dimerization‐mediated receptor activation via the complementary‐mediated strand displacement reaction‐induced dynamic DNA assembly. The sequence programmability of miRNA‐CDR allows it to sense and respond to a user‐defined miRNA with tunable sensitivity. Moreover, the miRNA‐CDR is versatile and customizable to reprogram desirable signaling output via adapting a designated receptor, such as MET and FGFR1. Using a mouse model of drug‐induced acute liver injury (DILI), we demonstrate the functionality of a designer miRNA‐CDR in rewiring the recognition of the DILI‐elevated miR‐122 to promote MET signaling of hepatocytes for biomarker‐driven in situ repair and liver function restoration. Our synthetic miRNA‐CDR platform provides a novel molecular device enabling biomarker‐driven therapeutic cellular response, potentially paving the way for improving the precision of cell therapy in regenerative medicine. [ABSTRACT FROM AUTHOR]

New representatives of 2,4,7‐trisubstituted 9,9‐dialkyl‐9H‐fluorenes were prepared and used for crystallographic investigations as well as initial binding studies towards metal ions and carbohydrates. The binding studies, which included 1H NMR spectroscopic titrations and fluorescence measurements, demonstrated the ability of the tested fluorene‐based compounds to act as complexing agents for ionic and neutral substrates. Depending on the nature of the subunits of the fluorene derivatives, "turn on" or "turn off" fluorescent chemosensors can be developed. Compounds composed of 4,6‐dimethylpyridin‐2‐yl‐aminomethyl moieties have the potential to be used as sensitive "turn‐on" chemosensors for some metal ions. [ABSTRACT FROM AUTHOR]

The detection of human serum albumin (HSA) is of significant clinical importance in disease diagnoses. In this work, polymer-based synthetic receptors are designed by incorporating Ag-ZnS microspheres in molecularly imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MIPs) for the gravimetric detection of HSA. Among different compositions of Ag-ZnS@MIPs, MIPs having methacrylic acid and ethylene glycol dimethacrylate volume ratio of 3:2 exhibit enhanced HSA sensitivity in the concentration range of 5–200 ng/mL. A remarkably low threshold limit of detection (LOD = 0.364 ng/mL) is achieved with quartz crystal microbalance (QCM) based gravimetric sensors. Furthermore, the Ag-ZnS@MIPs/QCM sensors show high selectivity for HSA compared to other proteins, e.g., bovine serum albumin (BSA), glycoprotein, ribonuclease, and lysozyme. Hence, the gravimetric quantification of HSA realizes a highly sensitive, selective, and label-free detection mechanism with a limit of quantification down to 1.1 ng/mL. [ABSTRACT FROM AUTHOR]

Molecularly imprinted polymers (MIPs) have gained growing interest among researchers worldwide, due to their key features that make these materials interesting candidates for implementation as receptors into sensor applications. In fact, MIP-based glucose sensors could overcome the stability issues associated with the enzymes present in commercial glucose devices. Various reports describe the successful development of glucose MIPs and their coupling to a wide variety of transducers for creating sensors that are able to detect glucose in various matrices. In this review, we have summarized and critically evaluated the different production methods of glucose MIPs and the different transducer technologies used in MIP-based glucose sensors, and analyzed these from a commercial point of view. In this way, this review sets out to highlight the most promising approaches in MIP-based sensing in terms of both manufacturing methods and readout technologies employed. In doing so, we aim at delineating potential future approaches and identifying potential obstacles that the MIP-sensing field may encounter in an attempt to penetrate the commercial, analytical market. [ABSTRACT FROM AUTHOR]

The paper is a self-review of works on development of new approaches to formation of mimics of receptor and catalytic sites of biological macromolecules in the structure of highly cross-linked polymer membranes and thin films. The general strategy for formation of the binding sites in molecularly imprinted polymer (MIP) membranes and thin films was described. A selective recognition of a number of food toxins, endocrine disruptors and metabolites is based on the results of computational modeling data for the prediction and optimization of their structure. A strategy proposed for the design of the artificial binding sites in MIP membranes was supported by the research performed by the authors on development of a number of the MIP membrane-based affinity and catalytic biosensors for selective and sensitive measurement (detection limits 0.3–100 nM) of the target analytes. Novel versatile approaches aimed at improving sensitivity of the developed biosensor systems were discussed.

A method for encrypting messages using engineered bacteria and different fluorescently labeled synthetic receptors is described. We show that the binding of DNA-based artificial receptors to E. coli expressing His-tagged outer membrane protein C (His-OmpC) induces a Förster resonance energy transfer (FRET) between the dyes, which results in the generation of a unique fluorescence fingerprint. Because the bacteria continuously divide, the emission pattern generated by the modified bacteria dynamically changes, enabling the system to produce encryption keys that change with time. Thus, this development indicates the potential contribution of live-cell-based encryption systems to the emerging area of information protection at the molecular level.

Abstract A series of new 9,9‐diethylfluorenes consisting of three side‐arms each bearing a heterocyclic, bis(carboxymethyl)amino, bis(carbamoylmethyl)amino, bis(ethoxycarbonylmethyl)amino or an amino group were prepared on the basis of 2,4,7‐tris(bromomethyl)‐9,9‐diethylfluorene. Imidazolyl, benzimidazolyl, pyrazolyl, pyrrolyl, 1,3‐dioxoisoindolyl and pyridinium groups were taken into account as heterocyclic units, attached to the aromatic skeleton via −CH2−, −CH2NHCH2− or −CH2N=CH− linkers. In addition to the seventeen 2,4,7‐trisubstituted 9,9‐diethylfluorenes, two macrocyclic compounds were prepared on the basis of 2,7‐bis(aminomethyl)‐9,9‐diethylfluorene. The excellent yield of the macrocyclization reaction is worth a special mention. Both the acyclic and the macrocyclic fluorene‐based compounds have, among other things, the potential to act as artificial receptors for different substrates in analogy to the known receptors consisting of a benzene or biphenyl core.

Abstract Artificial receptor‐based protein assays have various attractive features such as a long‐term stability, a low‐cost production process, and the ease of tuning the target specificity. However, such protein sensors are still immature compared with conventional immunoassays. To enhance the application potential of synthetic sensing materials, organic field‐effect transistors (OFETs) are some of the suitable platforms for protein assays because of their solution processability, durability, and compact integration. Importantly, OFETs enable the electrical readout of the protein recognition phenomena of artificial receptors on sensing electrodes. Thus, we believe that OFETs functionalized with artificial protein receptors will be a powerful tool for the on‐site analyses of target proteins. In this Minireview, we summarize the recent progress of the OFET‐based protein assays including the rational design strategies for devices and sensing materials.

The detection of human serum albumin (HSA) is of significant clinical importance in disease diagnoses. In this work, polymer-based synthetic receptors are designed by incorporating Ag-ZnS microspheres in molecularly imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MIPs) for the gravimetric detection of HSA. Among different compositions of Ag-ZnS@MIPs, MIPs having methacrylic acid and ethylene glycol dimethacrylate volume ratio of 3:2 exhibit enhanced HSA sensitivity in the concentration range of 5–200 ng/mL. A remarkably low threshold limit of detection (LOD = 0.364 ng/mL) is achieved with quartz crystal microbalance (QCM) based gravimetric sensors. Furthermore, the Ag-ZnS@MIPs/QCM sensors show high selectivity for HSA compared to other proteins, e.g., bovine serum albumin (BSA), glycoprotein, ribonuclease, and lysozyme. Hence, the gravimetric quantification of HSA realizes a highly sensitive, selective, and label-free detection mechanism with a limit of quantification down to 1.1 ng/mL.

Molecularly imprinted polymers (MIPs) have gained growing interest among researchers worldwide, due to their key features that make these materials interesting candidates for implementation as receptors into sensor applications. In fact, MIP-based glucose sensors could overcome the stability issues associated with the enzymes present in commercial glucose devices. Various reports describe the successful development of glucose MIPs and their coupling to a wide variety of transducers for creating sensors that are able to detect glucose in various matrices. In this review, we have summarized and critically evaluated the different production methods of glucose MIPs and the different transducer technologies used in MIP-based glucose sensors, and analyzed these from a commercial point of view. In this way, this review sets out to highlight the most promising approaches in MIP-based sensing in terms of both manufacturing methods and readout technologies employed. In doing so, we aim at delineating potential future approaches and identifying potential obstacles that the MIP-sensing field may encounter in an attempt to penetrate the commercial, analytical market.

Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the traditional analytical chemistry methods for sucrose quantification in plants require sample treatment (with consequent tissue destruction) and complex facilities, that do not allow real-time sucrose quantification at ultra-low concentrations (nM to pM range) under in vivo conditions, limiting our understanding of sucrose roles in plant physiology across different plant tissues and cellular compartments. Some of the above-mentioned problems may be circumvented with the use of bio-compatible ligands for molecular recognition of sucrose. Nevertheless, problems such as the signal-noise ratio, stability, and selectivity are some of the main challenges limiting the use of molecular recognition methods for the in vivo quantification of sucrose. In this review, we provide a critical analysis of the existing analytical chemistry tools, biosensors, and synthetic ligands, for sucrose quantification and discuss the most promising paths to improve upon its limits of detection. Our goal is to highlight the criteria design need for real-time, in vivo, highly sensitive and selective sucrose sensing capabilities to enable further our understanding of living organisms, the development of new plant breeding strategies for increased crop productivity and sustainability, and ultimately to contribute to the overarching need for food security.

Abstract The design of a fully synthetic, chemical “apoptosis‐inducing receptor” (AIR) molecule is reported that is anchored into the lipid bilayer of cells, is activated by the incoming biological input, and responds with the release of a secondary messenger—a highly potent toxin for cell killing. The AIR molecule has four elements, namely, an exofacial trigger group, a bilayer anchor, a toxin as a secondary messenger, and a self‐immolative scaffold as a mechanism for signal transduction. Receptor installation into cells is established via a robust protocol with minimal cell handling. The synthetic receptor remains dormant in the engineered cells, but is effectively triggered externally by the addition of an activating biomolecule (enzyme) or in a mixed cell population through interaction with the surrounding cells. In 3D cell culture (spheroids), receptor activation is accessible for at least 5 days, which compares favorably with other state of the art receptor designs.

The design of a fully synthetic, chemical "apoptosis‐inducing receptor" (AIR) molecule is reported that is anchored into the lipid bilayer of cells, is activated by the incoming biological input, and responds with the release of a secondary messenger—a highly potent toxin for cell killing. The AIR molecule has four elements, namely, an exofacial trigger group, a bilayer anchor, a toxin as a secondary messenger, and a self‐immolative scaffold as a mechanism for signal transduction. Receptor installation into cells is established via a robust protocol with minimal cell handling. The synthetic receptor remains dormant in the engineered cells, but is effectively triggered externally by the addition of an activating biomolecule (enzyme) or in a mixed cell population through interaction with the surrounding cells. In 3D cell culture (spheroids), receptor activation is accessible for at least 5 days, which compares favorably with other state of the art receptor designs. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is a clinically validated target for a multitude of human cancers. The receptor is activated upon ligand binding through a critical dimerization step. Dimerization can be replicated in vitro by locally concentrating the receptor kinase domains on the surface of lipid‐based vesicles. In this study we investigated the use of coiled coils to induce spontaneous receptor kinase domain dimerization in vitro to form non‐membrane‐bound artificial receptor mimics in solution. Two engineered forms of EGFR kinase domain fused to coiled coil complementary peptides were designed to self‐associate upon mixing. Two fusion protein species (P3‐EGFR and P4‐EGFR) independently showed the same activity and polymerization profile known to exist with EGFR kinase domains. Upon mixing the two species, coiled coil heterodimers were formed that induced EGFR association to form dimers of the kinase domains. This was accompanied by 11.5‐fold increase in the phosphorylation rate indicative of kinase domain activation equivalent to the levels achieved using vesicle localization and mimicking in vivo ligand‐induced activation. This study presents a soluble tyrosine kinase receptor mimic capable of spontaneous in vitro activation that can facilitate functional and drug discovery studies for this clinically important receptor class. [ABSTRACT FROM AUTHOR]

Abstract The newest generation of cell‐based technologies relies heavily on methods to communicate to the engineered cells using artificial receptors, specifically to deactivate the cells administered to a patient in the event of adverse effects. Herein, artificial synthetic internalizing receptors are engineered that function in mammalian cells in 2D and in 3D and afford targeted, specific intracellular drug delivery with nanomolar potency in the most challenging cell type, namely primary, donor‐derived T cells. Receptor design comprises a lipid bilayer anchor for receptor integration into cell membrane and a small xenobiotic molecule as a recognition ligand. Artificial receptors are successfully targeted by the corresponding antibody–drug conjugate (ADC) and exhibit efficient cargo cell entry with ensuing intracellular effects. Receptor integration into cells is fast and robust and affords targeted cell entry in under 2 h. Through a combination of the receptor design and the use of ADC, combined benefits previously made available by chimeric artificial receptors (performance in T cells) and the chemical counterpart (robustness and simplicity) in a single functional platform is achieved. Artificial synthetic receptors are poised to facilitate the maturation of engineered cells as tools of biotechnology and biomedicine.

A series of new 9,9‐diethylfluorenes consisting of three side‐arms each bearing a heterocyclic, bis(carboxymethyl)amino, bis(carbamoylmethyl)amino, bis(ethoxycarbonylmethyl)amino or an amino group were prepared on the basis of 2,4,7‐tris(bromomethyl)‐9,9‐diethylfluorene. Imidazolyl, benzimidazolyl, pyrazolyl, pyrrolyl, 1,3‐dioxoisoindolyl and pyridinium groups were taken into account as heterocyclic units, attached to the aromatic skeleton via −CH2−, −CH2NHCH2− or −CH2N=CH− linkers. In addition to the seventeen 2,4,7‐trisubstituted 9,9‐diethylfluorenes, two macrocyclic compounds were prepared on the basis of 2,7‐bis(aminomethyl)‐9,9‐diethylfluorene. The excellent yield of the macrocyclization reaction is worth a special mention. Both the acyclic and the macrocyclic fluorene‐based compounds have, among other things, the potential to act as artificial receptors for different substrates in analogy to the known receptors consisting of a benzene or biphenyl core. [ABSTRACT FROM AUTHOR]

This Minireview covers the latest developments of chemosensors based on transition‐metal receptors and organic fluorophores with specific binding sites for the luminescent detection and recognition of iodide in aqueous media and real samples. In all selected examples within the last decade (made‐post 2010), the iodide sensing and recognition is probed by monitoring real‐time changes of the fluorescence or phosphorescence properties of the chemosensors. This review highlights effective strategies to iodide sensing from a structural approach where the iodide recognition/sensing process, through supramolecular interactions as coordination bonds, hydrogen bonds, halogen bonds and electrostatic interactions, is transduced into an optical change easily measurable. The selective iodide sensing is an active field of research with global interest due to the importance of iodide in biological, medicinal, industrial, environmental and chemical processes. [ABSTRACT FROM AUTHOR]

The newest generation of cell‐based technologies relies heavily on methods to communicate to the engineered cells using artificial receptors, specifically to deactivate the cells administered to a patient in the event of adverse effects. Herein, artificial synthetic internalizing receptors are engineered that function in mammalian cells in 2D and in 3D and afford targeted, specific intracellular drug delivery with nanomolar potency in the most challenging cell type, namely primary, donor‐derived T cells. Receptor design comprises a lipid bilayer anchor for receptor integration into cell membrane and a small xenobiotic molecule as a recognition ligand. Artificial receptors are successfully targeted by the corresponding antibody–drug conjugate (ADC) and exhibit efficient cargo cell entry with ensuing intracellular effects. Receptor integration into cells is fast and robust and affords targeted cell entry in under 2 h. Through a combination of the receptor design and the use of ADC, combined benefits previously made available by chimeric artificial receptors (performance in T cells) and the chemical counterpart (robustness and simplicity) in a single functional platform is achieved. Artificial synthetic receptors are poised to facilitate the maturation of engineered cells as tools of biotechnology and biomedicine. [ABSTRACT FROM AUTHOR]

Artificial receptor‐based protein assays have various attractive features such as a long‐term stability, a low‐cost production process, and the ease of tuning the target specificity. However, such protein sensors are still immature compared with conventional immunoassays. To enhance the application potential of synthetic sensing materials, organic field‐effect transistors (OFETs) are some of the suitable platforms for protein assays because of their solution processability, durability, and compact integration. Importantly, OFETs enable the electrical readout of the protein recognition phenomena of artificial receptors on sensing electrodes. Thus, we believe that OFETs functionalized with artificial protein receptors will be a powerful tool for the on‐site analyses of target proteins. In this Minireview, we summarize the recent progress of the OFET‐based protein assays including the rational design strategies for devices and sensing materials. [ABSTRACT FROM AUTHOR]

For many decades, synthetic receptors have been used as sensor elements and are a promising alternative to natural receptors, which, despite its great selectivity, are so complex and instable. The rational design of this kind of receptors is currently one of the most researched topics in molecular recognition. Molecular imprinted polymers (MIPs) have become a growing highlight in polymer chemistry, once they possess a wide range of applications and can be used in several environments, due to their high chemical and thermal stability. The aim of this study was to perform a rational design for the MIP preparation, for 3,4-methylenedioxymethamphetamine (MDMA) detection. The theoretical measurements were employed at several stages of the process, using DFT and B3LYP/6-31G(d,p) level of theory, by means of optimization and frequency calculations. Among the several functional monomers tested, the itaconic acid was the most appropriated for MIP preparation with MDMA template, and the proper molar ratio found theoretically was 3:1 (itaconic acid/MDMA). In the preparation of pre-polymerization complex, polar solvents were found to perform a better stabilization, mainly those which are not protic solvents. As cross-linking agents, the better results were obtained for trimethylolpropane trimethacrylate and ethylene glycol dimethacrylate molecules, respectively. Finally, selectivity tests showed a high affinity of the studied MIP for MDMA and chemically similar molecules. The proposal theoretical strategy yielded novel, experimentally testable hypotheses for the design of MIPs. Additionally, from the theoretical point of view, the set of computational analyses presented in this paper constitutes a very useful protocol to predict optimal experimental conditions, which can considerably reduce the time and cost on the MIPs preparation. [ABSTRACT FROM AUTHOR]

Highly efficient transmembrane transport of exogenous reagents into cells is of vital importance for developing drug‐delivery systems. Conventionally, transmembrane transport of exogenous reagents was accomplished with the assistance of transfection agents or other artificial means. However, the high toxicity and low transport efficiency of current delivery techniques still remain to be solved. In this work, by anchoring artificial receptors onto cell membranes with a mild chemical reaction, we demonstrated that the exogenous reagent framework nucleic acids, namely tetrahedral DNA nanostructures (TDN) can bind onto cell membranes effectively by the hybridization between single‐stranded DNA (ssDNA) and pendant ssDNA of TDN. The transport rate was greatly enhanced, with the endocytosis time could be as fast as 0.5 h. Furthermore, the transport quantity was prominently improved, with around 30 % of TDN endocytosed within 4 h. Owing to its rapid transmembrane transport speed and improved endocytosis quantity, this artificial‐receptor‐mediated transmembrane transport is a promising tool for achieving rapid and highly efficient transmembrane transport of exogenous reagents. [ABSTRACT FROM AUTHOR]

In this work, surface magnetic molecularly imprinted polymers (SMMIPs) were synthesized and used as artificial receptors in the dispersive magnetic solid phase extraction (DMSPE) for capturing potential neuronal nitric oxide synthase–post synaptic density protein-95 (nNOS–PSD-95) uncouplers, which is known as neuroprotection against stroke. Factors that affected selective separation and adsorption of the artificial receptors, such as the amount of template, the types of functional monomer and porogen solvents, and the molar ratio of template/functional monomer/cross-linker were optimized. The artificial receptors were also characterized using fourier transformed infrared, scanning electron microscope, thermal gravimetric analysis and physical property measurement systems. Multiple interactions between template and SMMIPs led to larger binding capacities, faster binding kinetics, quicker separation abilities and more efficient selectivity than the surface magnetic nonimprinted polymers (SMNIPs). The SMMIPs were successfully applied to capture potential nNOS–PSD-95 uncouplers from complex samples, and eight compounds were seized and confirmed rapidly when combined with HPLC and MS. The detection of the new nNOS–PSD-95 uncouplers ranged from 0.001 to 1.500 mg/mL with correlation coefficients of 0.9990–0.9995. The LOD and LOQ were 0.10–0.68 μg/mL and 0.47–2.11 μg/mL, respectively. The neuroprotective effect and co-immunoprecipitation test in vitro revealed that Emodin-1- O -β- d -glucoside, Rhaponticin, Gnetol and 2,3,5,4′-Tetrahydroxystilbene-2- O -β- d -glucoside have neuroprotective and uncoupling activities, and that they may be the new uncouplers of nNOS–PSD-95 [ABSTRACT FROM AUTHOR]

Peptide based lectin mimetics represent an attractive approach for the development of artificial carbohydrate receptors that might find application in bio-analytical and medicinal fields. Taking into consideration the structure of typical lectin binding site, we have designed a novel artificial receptor molecule possessing a rigid three-dimensional structure, hydrogen-bonding site and lipophilic binding pocket to promote hydrophobic interaction and hydrogen-bonding. A new solid-phase synthetic approach that allows complete synthesis of desired bicyclic peptide 1 on the solid support was developed. CD spectra of peptides 1 and 2 indicate that the structure of 1 is rather rigid and preorganised for the three-dimensional monosaccharide substrates binding. The binding affinities of bicyclic peptide receptor 1 toward various carbohydrate substrates at physiologically relevant conditions were estimated by UV/vis and fluorimetric titration experiments, and the observed values are in the millimolar range. With these results we have demonstrated that the bicyclic peptide 1 represent a promising basis for the design of new and more efficient carbohydrate receptors that may have broader application in bio-analytical or medicinal field. [ABSTRACT FROM AUTHOR]

In this paper for the first time we successfully detect bacterial flagellar filaments from Proteus mirabilis using molecularly imprinted artificial receptors. These receptors acted as a sensing layer of the biosensors, assembled by imprinting flagellar proteins onto a polymeric backbone of electropolymerized phenol. In short, flagellar filaments were absorbed onto a carbon support, phenol was electropolymerized around it through the carbon conductive matrix to create the protein molecular molds, and finally the flagellar proteins were removed by enzymatic and electrochemical action. Each removed flagellar protein gave rise to an imprinted site with eventual rebinding ability. Electrical impedance spectroscopy (EIS) and square wave voltammetry (SWV) were employed to measure the interaction of flagellar filaments with the sensing layer assembled on commercial screen-printed electrodes, providing low detection limits, high precision and selectivity toward the targeted protein. The detection limit was 0.7 ng/mL by EIS and 0.9 ng/mL by SWV. The artificial receptors were further assembled on home-made paper-printed electrodes, with the three-electrode system printed on a paper substrate, offering the possibility of detecting flagellar filaments at as low as 0.6 ng/mL with a disposable and cost-effective portable device. To the best of our knowledge this is the first sensing device where molecularly imprinted artificial receptors are tailored on home-made electrode based on paper substrates with three electrodes assembled together, which is a suitable approach for the fabrication of easy and cost-effective tailored electrodes. [ABSTRACT FROM AUTHOR]

The series of macroporous monolithic molecularly imprinted monoliths differed by pore size, column length (volume) and amount of template used for imprinting was synthesized using methacrylic acid and glycerol dimethacrylate as co-monomers and antibiotic ciprofloxacin as a template. The prepared monoliths were characterized regarding to their permeability, pore size, porosity, and resistance to the flow of a mobile phase. The surface morphology was also analyzed. The slight dependence of imprinting factor on flow rate, as well as its independence on pore size of macroporous molecularly imprinted monolithic media was observed. The column obtained at different conditions exhibited different affinity of ciprofloxacin to the imprinted sites that was characterized with K diss values in the range of 10 −5 –10 −4 M. The solid-phase extraction of ciprofloxacin from such biological liquids as human blood serum, human urine and cow milk serum was performed using the developed monolithic columns. In all cases, the extraction was found to be 95.0–98.6%. Additionally, the comparison of extraction of three fluoroqinolone analogues, e.g. ciprofloxacin, levofloxacin and moxifloxacin, from human blood plasma was carried out. Contrary to ciprofloxacin extracted with more than 95%, this parameter did not exceed 40% for its analogues. [ABSTRACT FROM AUTHOR]

The synthesis of macroporous molecularly imprinted monoliths was performed using the monomers system 2-hydroxyethyl methacrylate-ethylene glycol dimethacrylate and erythromycin as a template. The copolymerization was carried out in situ inside 50 mm × 4.6 mm i.d. stainless-steel tubing. The morphology of the monoliths was examined with scanning electron microscopy. The porous characteristics were determined both from the data of hydrodynamic permeability of monoliths and by means of mercury intrusion porosimetry. The retention parameters of target substance (erythromycin), values of calculated imprinting factors and apparent dynamic dissociation constants were obtained for monoliths prepared with the application of different amount of template (4, 8 and 12 mol%). The separations of the mixtures azithromycin/erythromycin and ciprofloxacin/erythromycin were demonstrated. Additionally, the possibility of erythromycin quantification in human blood plasma was shown. [ABSTRACT FROM AUTHOR]

In terms of the thermodynamics of solutions (using the density functional theory (DFT) method at RwB97XD/6-31G(d) level of the theory) the influence of the environment, as well as type of functional monomers and a ratio of "template molecule (melamine) to monomer molecules" on the recognition properties of pre-polymerization complexes of "artificial receptor" against melamine has been explored. The geometries and energy characteristics of the "functional monomer-template" pre-polymerization complexes with the ratios 1:1, 2:1, 3:1 were obtained. There are acrylamido-2-methyl-1-propanesulfonic acid (AMPSA), ethylene glycol methacrylate phosphate, itaconic acid and acrylic acids were considered as functional monomers. It is shown that for all environments and there is a pattern, namely, the most energetically favorable monomer in the formation of pre-polymerization complexes with melamine is AMPSA. It is followed by itaconic and acrylic acid. In addition, the same sequence is stored at increase of the ratio between the molecules of monomers and melamine. [ABSTRACT FROM AUTHOR]

Glycoproteins are closely associated with the occurrence of diverse diseases, and they have been used as biomarkers and therapeutic targets in clinical diagnostics. Currently, mass spectrometry has proven to be a powerful tool for glycoprotein analysis, but it is almost impossible to directly identify glycoproteins without the preparation and pretreatment of samples. Furthermore, biological samples, especially proteins, are damaged by this process. Herein, we describe a novel fluorescence nanosensor based on a molecularly imprinted spatial structure and boronate affinity that is wellsuited for monitoring glycoproteins selectively. Results showed that the recognition performance of the nanosensor for glycoproteins was regulated by controlling the pH value and temperature. Moreover, the nanosensor was successfully applied to the detection of HRP in biological fluids. This study provides a facile and efficient fluorescence tool for glycoprotein detection in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Abstract: A new type of molecularly imprinted polymer (MIP)-based fluorescent artificial receptor was developed by anchoring MIP on the surface of denatured bovine serum albumin (dBSA) modified CdTe quantum dots (QDs) using the surface molecular imprinting process. The approach combined the merits of molecular imprinting technology and the fluorescent property of the CdTe QDs. The dBSA was used not only to modify the surface defects of the CdTe QDs, but also as assistant monomer to create effective recognition sites. Three different proteins, namely lysozyme (Lyz), cytochrome c (Cyt) and methylated bovine serum albumin (mBSA), were tested as the template molecules and then the receptors were synthesized by sol–gel reaction (imprinting process). The results of fluorescence and binding experiments demonstrated the recognition performance of the receptors toward the corresponding template. Under optimum conditions, the linear range for Lyz was from 1.4×10−8 to 8.5×10−6 M, and the detection limit was 6.8nM. Moreover, the new artificial receptors were applied to separate and detect Lyz in real samples. This fluorescent artificial receptor may serve as a starting point in the design of highly effective synthetic fluorescent receptor for recognition of target protein. [Copyright &y& Elsevier]

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented. [ABSTRACT FROM AUTHOR]

Integrins play a pivotal role in cell-cell adhesion, signalling and apoptosis. Many extracellular proteins use the RGD sequence (arginine-glycine-aspartate) as a key to dock onto and unlock their respective binding partners at the cell membrane (αVβ3-, aIIbβ3- and a5β1-integrin). Here, the RGD signal is transduced into the cytoplasm and triggers a variety of biological events such as blood coagulation, cell-matrix binding, cell differentiation and angiogenesis. A misfunction of this recognition system causes severe diseases, rendering the RGD recognition system an attractive drug target. Inhibition of RGD-integrin interactions can be reached in two different ways, by blocking integrins with RGD mimetics or by capping RGD-containing proteins by artificial RGD receptors. This review provides an overview over the very young history of artificial RGD receptor development, beginning with early research in arginine recognition, over the discovery of the first primitive RGD receptor until the present state of research and future prospects. [ABSTRACT FROM AUTHOR]

Abstract: Metalloporphyrins offer almost unique opportunities to design artificial receptors for chemical sensors. These molecules can be tailored, at the synthetic level, changing in a almost controlled way the sensor selectivity that can be oriented toward desired analyte families. Optical and electrochemical properties of metalloporphyrins are known since several years and they have been adequately exploited as potentiometric sensors for ions in solutions. In gas sensing the optical characteristics were utilized to detect gases like O2 and NO2 for which metalloporphyrins have a good selectivity. In gas environment, beside these gases the interactions are very rich but rather unselective, nonetheless this feature is interesting for artificial olfaction where a certain degree of cross-selectivity is required. As a consequence, arrays of gas sensors based on metalloporphyrins and optical and mass transducers have been demonstrated in the last decade. In this paper the properties of such arrays are reviewed evidencing the high flexibility of such sensors and their wide spectrum of applications. [Copyright &y& Elsevier]

Abstract: This review covers the field of anion recognition from the perspective of tetrahedral oxyanion recognition. The bulk of the attention is devoted to metal-free systems that are able to effect the recognition, binding or transport of phosphate and sulfate. Particular emphasis is devoted to design criteria that allow for discrimination and selectivity. In this context, a variety of recognition motifs are discussed and, within each receptor class, general paradigms that allow for the construction of receptor systems with high affinity and specificity are noted. [Copyright &y& Elsevier]

Abstract: An Fmoc-protected δ-sugar amino acid, prepared by oxidation of a glucosamine derivative, was coupled to three different tripeptide tert-butyl esters (H-Tyr-Tyr-Tyr-OtBu, H-Tyr-Glu(OBzl)-Tyr-OtBu and H-Tyr-Arg(Mtr)-Tyr-OtBu) and the resulting sugar amino acid/amino acid hybrids were transformed into dimers that were subsequently cyclized to give three C2-symmetric macrocycles. The macrocycles were deprotected and their binding properties towards p-nitrophenyl glycosides, nucleotides, and purines were examined. Of the ligands screened, only some of the purines showed weak, but significant, binding. [Copyright &y& Elsevier]

Binding mode calculations for complexes between an artificial paracyclophane receptor and digoxins, cholic acids as well as cortisone steroids show encapsulation of different ring combinations. Docking experiments were performed between the 26-10 antibody and digoxins. Coordination affinity arises from hydrophobic desolvation and van der Waals interactions rather than from hydrogen bonds. The specificity and affinity arises mainly from shape complementarity. Computed binding free energies and Kohonen neural network computations both point to physicochemical and structural similarities of natural antibodies and artificial receptors. [ABSTRACT FROM AUTHOR]

The electrostatic potential surface (EPS) is calculated for molecular tweezers, clips, and bowls at different levels of theory (semiempirical AM1, ab initio HF/6-31G*, and density functional theory pBP/DN**). According to these calculations, the molecular electrostatic potential (MEP) on the concave side of the molecular tweezers and clips is suprisingly negative for hydrocarbons. This finding seems to be a general phenomenon in nonconjugated π-electron systems with concave-convex topology and it explains the receptor properties of the molecular tweezers and clips. Analogous calculations performed for the conjugated aromatic molecular bowls show different results. The DFT calculations predict that in these systems the more negative MEP lies on the concave side similar to the findings for the nonconjugated molecular tweezer- and clip-systems, whereas the AM1 calculation leads to the opposite result that the MEP is more negative on convex side of the bowl-systems. [ABSTRACT FROM AUTHOR]

In the study, we have developed an efficient and robust method using dual modes of fluorescence sensing and smartphone readout for the detection of pyrethroids using artificial receptors inside a covalent organic framework. Carbazole-conjugated frameworks (CCFs) were used to prepare efficient fluorescent probes that combine stability with light-emitting activity. C N linkages between aldehydes and amines formed Schiff bases, allowing the development of layered structures, creating exceptionally stable frameworks. Artificial receptors that can bind compounds inside the CCFs with high affinity, for both the detection and absorption of λ-cyhalothrin (LC), were constructed using room-temperature reverse microemulsion polymerization. Under optimum conditions, the fluorescence sensing correlation with the concentration of LC showed good linearity in the range of 0.8–175 μg L−1 with a detection limit of 0.368 μg L−1. The smartphone-based visible readout exhibited a good effect, with a detection limit of 4.067 μg L−1, and recovery of 88 %–103% in food samples. A parallel analysis in food samples was conducted by high-performance liquid chromatography, the results showed good consistency, indicating the practicability of the developed method. Dual mode analysis can avoid the disadvantages of a single response, providing excellent sensitivity, specificity, and efficiency through a strong binding force between the target and the artificial receptors. [Display omitted] • Efficient and robust dual modes of fluorescence sensing and smartphone readout for the detection of pyrethroids. • Dual mode analysis using artificial receptors bound inside a covalent organic framework. • Carbazole-conjugated frameworks were used to prepare efficient fluorescent probes. • The on/off fluorescence of the target-CCFs complex was reversible. • Dual mode analysis provide excellent sensitivity, specificity, and efficiency. [ABSTRACT FROM AUTHOR]

A robust and highly specific sensor based on electroactive molecularly imprinted polymer nanoparticles (nanoMIP) was developed. The nanoMIP tagged with a redox probe, combines both recognition and reporting capabilities. The developed nanoMIP replaces enzyme-mediator pairs used in traditional biosensors thus, offering enhanced molecular recognition for insulin, improving performance in complex biological samples, and yielding high stability. Also, most of existing sensors show poor performance after storage. To improve costs of the logistics and avoid the need of cold storage in the chain supply, we developed an alternative to biorecognition system that relies on nanoMIP. NanoMIP were computationally designed using "in-silico" insulin epitope mapping and synthesized by solid phase polymerisation. The characterisation of the polymer nanoparticles was performed by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform Infrared (FT-IR) and surface plasmon resonance (SPR). The electrochemical sensor was developed by chemical immobilisation of the nanoMIP on screen printed platinum electrodes. The insulin sensor displayed satisfactory performances and reproducible results (RSD = 4.2%; n = 30) using differential pulse voltammetry (DPV) in the clinically relevant concentration range from 50 to 2000 pM. The developed nanoMIP offers the advantage of large number of specific recognition sites with tailored geometry, as the resultant, the sensor showed high sensitivity and selectivity to insulin with a limit of detection (LOD) of 26 and 81 fM in buffer and human plasma, respectively, confirming the practical application for point of care monitoring. Moreover, the nanoMIP showed adequate storage stability of 168 days, demonstrating the robustness of sensor for several rounds of insulin analysis. • The molecularly imprinted polymer nanoparticles tagged with a redox probe, combines both recognition and reporting functions. • The electroactive nanoparticles system replaces enzyme-mediator pairs used in classic biosensors. • Nanoparticles were computationally designed to selectively bind insulin epitopes. • The sensor devised provides adequate selectivity, low cross-reactivity and high sensitivity in plasma. • This technology is robust and can be potentially applied to a broad range of targets. [ABSTRACT FROM AUTHOR]

Phenolic compounds are secondary metabolites frequently found in plants that exhibit many different effects on human health. Because of the relevant bioactivity, their identification and quantification in agro-food matrices as well as in biological samples are a fundamental issue in the field of quality control of food and food supplements, and clinical analysis. In this review, a critical selection of sensors and biosensors for rapid and selective detection of phenolic compounds is discussed. Sensors based on electrochemistry, photoelectrochemistry, fluorescence, and colorimetry are discussed including devices with or without specific recognition elements, such as biomolecules, enzymes and molecularly imprinted materials. Systems that have been tested on real matrices are prevalently considered but also techniques that show potential development in the field. [ABSTRACT FROM AUTHOR]

Synthetic sensing materials (artificial receptors) are some of the most attractive components of chemical/biosensors because of their long-term stability and low cost of production. However, the strategy for the practical design of these materials toward specific molecular recognition in water is not established yet. For the construction of artificial material-based chemical/biosensors, the bottom-up assembly of these materials is one of the effective methods. This is because the driving forces of molecular recognition on the receptors could be enhanced by the integration of such kinds of materials at the 'interfaces', such as the boundary portion between the liquid and solid phases. Additionally, the molecular assembly of such self-assembled monolayers (SAMs) can easily be installed in transducer devices. Thus, we believe that nanosensor platforms that consist of synthetic receptor membranes on the transducer surfaces can be applied to powerful tools for high-throughput analyses of the required targets. In this review, we briefly summarize a comprehensive overview that includes the preparation techniques for molecular assemblies, the characterization methods of the interfaces, and a few examples of receptor assembly-based chemical/biosensing platforms on each transduction mechanism. [ABSTRACT FROM AUTHOR]