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This review describes the analytical methods that have been developed over the years to tackle the high polarity and non-chromophoric nature of amino acids (AAs). First, the historical methods are briefly presented, with a strong focus on the use of derivatization reagents to make AAs detectable with spectroscopic techniques (ultraviolet and fluorescence) and/or sufficiently retained in reversed phase liquid chromatography. Then, an overview of the current analytical strategies for achiral separation of AAs is provided, in which mass spectrometry (MS) becomes the most widely used detection mode in combination with innovative liquid chromatography or capillary electrophoresis conditions to detect AAs at very low concentration in complex matrixes. Finally, some future trends of AA analysis are provided in the last section of the review, including the use of supercritical fluid chromatography (SFC), multidimensional liquid chromatography and electrophoretic separations, hyphenation of ion exchange chromatography to mass spectrometry, and use of ion mobility spectrometry mass spectrometry (IM-MS). Various application examples will also be presented throughout the review to highlight the benefits and limitations of these different analytical approaches for AAs determination.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Biosensors are a promising tool offering the possibility of low cost and fast analytical screening in point-of-care diagnostics and for on-site detection in the field. Most biosensors in routine use ensure their selectivity/specificity by including natural receptors as biorecognition element. These materials are however too expensive and hard to obtain for every biochemical molecule of interest in environmental and clinical practice. Molecularly imprinted polymers have emerged through time as an alternative to natural antibodies in biosensors. In theory, these materials are stable and robust, presenting much higher capacity to resist to harsher conditions of pH, temperature, pressure or organic solvents. In addition, these synthetic materials are much cheaper than their natural counterparts while offering equivalent affinity and sensitivity in the molecular recognition of the target analyte. Imprinting technology and biosensors have met quite recently, relying mostly on electrochemical detection and enabling a direct reading of different analytes, while promoting significant advances in various fields of use. Thus, this review encompasses such developments and describes a general overview for building promising biomimetic materials as biorecognition elements in electrochemical sensors. It includes different molecular imprinting strategies such as the choice of polymer material, imprinting methodology and assembly on the transduction platform. Their interface with the most recent nanostructured supports acting as standard conductive materials within electrochemical biomimetic sensors is pointed out.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The glycine fragment in the nickel(II) complex (1) formed from the Schiff’s base of glycine and (S)-o-<(N-benzylprolyl)amino>benzophenone (2) undergoes base-catalysed Michael addition to acrylaldehyde, alpha-methylacrylaldehyde, (E)-crotonaldehyde, (E)-cinnamaldehyde, and methyl vinyl ketone.No products of 1,2-addition were found in the Et3N-catalysed reactions.Addition followed by epimerization of the isomeric complexes proceeds with high diastereoselectivity at Calpha (90percent) and Cbeta of the corresponding amino acid side chains.After chromatographic separation, the diastereoisomerically pure complexes were decomposed and the resulting dihydropyrrole-2-carboxylic acids reduced with NaBH3CN to give (S)-proline, trans-3-methyl-(S)-proline, trans-5-phenyl-(S)-proline, and a mixture of cis- and trans-5-methyl-(S)-prolines.The chiral auxiliary (2) was recovered in 80-90percent yield.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Antibiotic resistance is a significant emerging health threat. Exacerbating this problem is the overprescription of antibiotics as well as a lack of development of new antibacterial agents. A paradigm shift toward the development of nonantibiotic agents that target the virulence factors of bacterial pathogens is one way to begin to address the issue of resistance. Of particular interest are compounds targeting bacterial AB toxins that have the potential to protect against toxin-induced pathology without harming healthy commensal microbial flora. Development of successful antitoxin agents would likely decrease the use of antibiotics, thereby reducing selective pressure that leads to antibiotic resistance mutations. In addition, antitoxin agents are not only promising for therapeutic applications, but also can be used as tools for the continued study of bacterial pathogenesis. In this review, we discuss the growing number of examples of chemical entities designed to target exotoxin virulence factors from important human bacterial pathogens.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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In this article, we describe the synthesis of imprinted chiral silica nanotubes based on the use of a chiral N-stearoyl l-serine (C18Ser) anionic surfactant as the chiral template. The resulting chiral silica nanotube structures were characterized by electronic microscopy (transmission electron microscopy (TEM) and scanning electron microscopy (SEM)) and nitrogen isotherms that proved the formation of well-ordered silica nanotubes. A C18Ser surfactant template was used for the preparation of the silica nanotubes, due to its effective molecular organization within the silica network. After chemical extraction of the chiral template, the enantioselectivity feature of the silica nanotubes was confirmed by selective adsorption of the enantiomers using circular dichroism (CD) and isothermal titration calorimetry (ITC) measurements. Although these measurements show a relatively low chiral selectivity of the silica nanotubes (ca. 6% enantiomeric excess), the system described here offers new approaches for the application of chiral porous materials in chirality.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The first synthesis of the cyclic peptide natural product, argadin is reported. Use of a solid-phase approach featuring side-chain resin attachment through histidine and a novel protecting group strategy allows rapid and efficient access to the argadin backbone, whereupon the unusual 3-amino-5-hydroxy-2-pyrrolidone moiety of the peptide is introduced by oxidative cyclisation of a homoserine residue. Argadin is shown to exist as a 5:1 mixture of diastereoisomers at the 5-hydroxy centre of the pyrrolidone ring, and inhibits a representative family-18 chitinase (ChiB1 from Aspergillus fumigatus) with Ki = 33 nM. The high-resolution X-ray crystal structure of synthetic argadin in complex with the same enzyme shows the binding of a single diastereoisomer as previously observed with the authentic natural product. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The asymmetric modularly designed supramolecular organocatalytic nitro olefin-ketone Michael addition of a variety of functionally rich nitro olefins with ketones was explored. The modularly designed supramolecular organocatalytic Michael reaction is characterized by a high rate, high chemoselectivity, high diastereoselectivity, high enantioselectivity, mild reaction conditions, readily available substrates/catalysts with simple operations, and excellent yields with a broad spectrum of functionally rich substrates. This method constitutes an alternative to previously known organocatalytic Michael reactions. We demonstrate the power of a supramolecular organocatalyst as an excellent stimulant for the highly reactive Michael addition of various ketones with functionally rich (E)-nitro olefins under ambient conditions to furnish enantiomerically pure carbamates and tetrahydroacridines; Cbz = benzyloxycarbonyl.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The intestines house a diverse microbiota that must compete for nutrients to survive, but the specific limiting nutrients that control pathogen colonization are not clearly defined. Clostridioides difficile colonization typically requires prior disruption of the microbiota, suggesting that outcompeting commensals for resources is critical to establishing C. difficile infection (CDI). The immune protein calprotectin (CP) is released into the gut lumen during CDI to chelate zinc (Zn) and other essential nutrient metals. Yet, the impact of Zn limitation on C. difficile colonization is unknown. To define C. difficile responses to Zn limitation, we performed RNA sequencing on C. difficile exposed to CP. In medium containing CP, C. difficile upregulated genes involved in metal homeostasis and amino acid metabolism. To identify CPresponsive genes important during infection, we measured the abundance of select C. difficile transcripts in a mouse CDI model relative to expression in vitro. Gene transcripts involved in selenium (Se)-dependent proline fermentation increased during infection and in response to CP. Increased proline fermentation gene transcription was dependent on CP Zn binding and proline availability, yet proline fermentation was only enhanced when Se was supplemented. CP-deficient mice could not restrain C. difficile proline fermentation-dependent growth, suggesting that CP-mediated Zn sequestration along with limited Se restricts C. difficile proline fermentation. Overall, these results highlight how C. difficile colonization depends on the availability of multiple nutrients whose abundances are dynamically influenced by the host response. IMPORTANCE Clostridioides difficile infection (CDI) is the leading cause of postantibiotic nosocomial infection. Antibiotic therapy can be successful, yet up to one-third of individuals suffer from recurrent infections. Understanding the mechanisms controlling C. difficile colonization is paramount in designing novel treatments for primary and recurrent CDI. Here, we found that limiting nutrients control C. difficile metabolism during CDI and influence overall pathogen fitness. Specifically, the immune protein CP limits Zn availability and increases transcription of C. difficile genes necessary for proline fermentation. Paradoxically, this leads to reduced C. difficile proline fermentation. This reduced fermentation is due to limited availability of another nutrient required for proline fermentation, Se. Therefore, CP-mediated Zn limitation combined with low Se levels overall reduce C. difficile fitness in the intestines. These results emphasize the complexities of how nutrient availability influences C. difficile colonization and provide insight into critical metabolic processes that drive the pathogen?s growth.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The discovery of vanadium’s insulin-like behaviour in vitro, and later of the orally available glucose- and lipid-lowering capability of these same compounds in vivo, has stimulated renewed interest in vanadium coordination chemistry. Besides the anti-diabetic effects for which it is now so well known, vanadium also exhibits a number of other therapeutic effects including anti-tumour and anti-inflammatory activities. In this review, emphasis will be on the most recent developments in the coordination chemistry of vanadium(III), (IV) and (V), as related to development of these compounds for pharmaceutical use. How best to measure bioactivity and the pharmaceutical relevance of accompanying increased oxidative stress will also be considered.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[11C] methoxyphenoxy)-2-methylpropanamide ([11C]8a), (S)-2-hydroxy-3-(2- [11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl) propanamide ([11C]8e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2- hydroxy-3-(4-[11C]methoxyphenoxy)-2-methylpropanamide ([ 11C]8c) and (S)-2-hydroxy-3-(4-[11C]methoxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([11C]8g), were prepared by O-[11C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2- hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy) -2-methylpropanamide (9c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4- nitro-3-(trifluoromethyl)phenyl)propanamide (9d), with [11C]CH 3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% (n = 5) radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/mumol (n = 5).

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI