This paper describes the development of a novel sorbent for selective extraction of endocrine disruptors (EDs) from aqueous media. The main goal was to obtain sufficient molecularly imprinted polymers (MIPs) for selective detection, preconcentration, and extraction of EDs such as bisphenol A (BPA) and progesterone (PG). Series of MIPs and their analogues, non-molecularly imprinted polymers (NIPs), were synthesised following a non-covalent imprinting strategy based on radical polymerisation. Sets of synthesis were performed in order to optimise variables of the polymerisation including solvent, cross-linker, and template ratio. The retention capacity of MIPs was determined using HPLC in the range of 33.3% to 96.6% and 32.5% to 96% for BPA and PG, respectively. The adsorption mechanism was studied by isothermal and kinetic assays. The kinetic analysis showed a high retention capacity within 15 min of contact. The polymer yield was obtained in the range of 30% to 100%. Additionally, there was no significant cross-reactivity observed upon testing MIPs with structural analogues and other endocrine disruptors instead of target molecules. The results also revealed the high importance of different concentrations of cross-linker and solvent during the polymerisation. Firstly, the pre-organisation of complementary functional groups, which were present in the polymerisation mixture, and secondly, selective cavity formation for target molecules.
The assay for cocaine based on molecularly imprinted nanoparticles prepared using solid phase approach is presented.
Microcystins (MCs) are dangerous cyanotoxins for the public health, and microcystin-LR (MC-LR) is one of most toxic, dangerous, and frequently found in water bodies. Typically, the detection of MCs is carried out by means of competitive ELISAs which, however, need special precautions for handling and storage, due to the stability of the antibodies used in this test. Molecularly imprinted nanoparticles (nanoMIPs) represents more robust and cost-effective alternative to antibodies. In this work, we developed a competitive pseudo-ELISA based on nanoMIPs (which are used in place of natural antibodies), for the detection of microcystin-LR (MC-LR). This pseudo-ELISA showed a linear response towards MC-LR, showing high affinity and low cross-reactivity against another analogue toxin (microcystin-YR). The analytical recovery of MC-LR in the analysis of water samples by the proposed pseudo-ELISA was 96 %–130 % and the limit of detection was 2.64 × 10−4 nM. The obtained results suggest that this competitive pseudo-ELISA could have high potential in the detection of toxins, due to its rapid, sensitive and accurate detection of toxin in water samples.
Laccase enzymes of were covalently coimmobilized on poly(glycidyl methacrylate) microspheres. The objective of this work was to create a biocatalyst that works efficiently in a wide range of pH. The coimmobilization was performed using two different strategies to compare the most efficient. The results showed that by correctly selecting the enzymes and concentrations involved in the commobilization, it is possible to obtain a biocatalyst that works efficiently at a wide pH range (2.0–7.0). The maximum activity values reached per gram of support for the obtained biocatalyst were 41.90 U (pH 3.0), 40.89 U (pH 4.0), and 39.54 U (pH 6.0). Moreover, the thermal, storage, and mechanical stabilities were improved compared to the free and single‐immobilized laccases. It was concluded that enzymatic coimmobilization is an excellent alternative to obtain a robust biocatalyst that works in a wide pH range, with potential environmental and industrial applications.
Nanoscale molecularly imprinted polymers (nano-MIPs) are powerful molecular recognition tools with broad applications in the diagnosis, prognosis, and treatment of complex diseases. In this work, fully atomistic molecular dynamics (MD) simulations are used to assist the design of nanoMIPs with recognition capacity toward L-fucose and D-mannose as prototype disease biomarkers. MD simulations were conducted on prepolymerization mixtures containing different molar ratios of the monomers N-isopropylacrylamide (NIPAM), methacrylamide (MAM), and (4acrylamidophenyl)(amino)methaniminium acetate (AB) and fixed molar ratios of the cross-linker ethylene glycol dimethacrylate (EGDMA) in explicit acetonitrile as the porogenic solvent. Prepolymerization mixtures containing ternary mixtures of NIPAM (50%), MAM (25%), and AB (25%) exhibit the best imprinting potential for both L-fucose and D-mannose, as they maximize (i) the stability of template-monomer plus template-cross-linker interactions, (ii) the number of functional monomers plus cross-linkers organized around the template, and (iii) the number of hydrogen bonds participating in template recognition. The studied prepolymerization mixtures exhibit an overall increased recognition capacity toward D-mannose over L-fucose, which is attributed to the higher hydrogen-bonding capacity of the former template. Our results are valuable to guide the synthesis of efficient nanoMIPs for sugar recognition and provide a computational framework extensible to any other template, monomer, or cross-linker combination, thus constituting a promising strategy for the rational design of molecularly imprinted materials.
Microtubule (MT) stabilization is an attractive pharmacological strategy to hamper the progress of neurodegenerative diseases. In this regard, seeking peptides with MT-stabilizing properties has awoken great interest. This work reports the rational discovery of two structurally related MT-stabilizing octapeptides using a combination of protein−peptide docking, conventional molecular dynamics, Gaussian accelerated molecular dynamics (GaMD), and tubulin polymerization assays. FASTA sequences for ∼1000 peptides were crafted from single and double mutants of davunetide (NAP) and docked against the Taxol (TX) site on an octameric MT model representing a portion of the MT wall. Docked peptides were rescored after MM minimization and binding free energy refinement through single-point MM/GBSA calculations. The 60 best-ranked peptides were subjected to 50 ns MD simulations on peptide−MT complexes at the terminal TX site in the octameric Tau−MT model resulting in 11 complexes with occupancies greater than 99% and peptide−protein binding free energies less than −40 kcal/mol. Selected peptides were then examined through 300 ns GaMD simulations in complexes containing two identical ligands at the terminal and intermediate TX sites in the Tau−MT model to account for the differential association of MTbinding peptides to different regions of the MT structure. Six candidates showed a favorable MT-binding potential based on the analysis of interaction frequencies and relative mobilities of the complex components, suggesting a pivotal role of Arg278, Gln281, and Arg369 residues for peptides recognition. Four candidates were predicted to preserve an adequate balance of longitudinal and lateral interactions between tubulin dimers in peptide−MT complexes such that MT-stabilizing effects could be expected. MT polymerization experiments confirmed that four peptides (HAPVSIHQ, NYPVSIHQ, NWPVSIWQ, HAPVSIIQ) exhibit MTstabilizing activity in vitro with NWPVSIWQ (P43) and HAPVSIIQ (P52) being the most active. Tryptophan quenching assays verified that P43 and P52 bind to nonpolymeric tubulin, whereas viability experiments on HEK cells confirmed their safety to pursue future pharmacological studies. The results herein presented are valuable to making progress in the rational design of MT-stabilizing peptides.
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