Search Results (12)

Amino acids (AAs), a type of nitrogen-based organic compounds in the atmosphere, are directly and indirectly related to climate change, and as their link to allergic diseases becomes more known, the need for quantitative analysis of ultrafine dust (PM_2.5) will become increasingly necessary. When sensing water-soluble AAs using a gas chromatograph combined with a tandem mass spectrometer (GC-MS/MS), derivatization should be considered to increase the volatility and sensitivity of target analytes. In this study, two methods were used to compare and evaluate 13 AA derivatives in PM_2.5 samples: N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide with 1% tert-butyldimethylchlorosilane (MTBSTFA w/1% t-BDMCS), which is preferred for silylation, and ethyl chloroformate (ECF) with methanol (MeOH) for chloroformate derivatization. The most appropriate reaction conditions for these two derivative methods, such as temperature and time, and the analytical conditions of GC-MS/MS for the qualitative and quantitative analysis of AAs were optimized. Furthermore, the calibration curve, detection limit, and recovery of both methods for validating the quantification were determined. The two derivative methods were applied to 23 actual PM_2.5 samples to detect and quantify target AAs. The statistical significances between pairwise measurements of individual AAs detected by both methods were evaluated. This study will help in selecting and utilizing appropriate derivative methods for the quantification of individual AAs in PM_2.5 samples. Full article

Background: The high global prevalence of prediabetes requires its early identification. Amino acids (AAs) have emerged as potential predictors of prediabetes. This study investigates the association between amino acids and prediabetes in the Kazakh population. Materials and Methods: In this case-control study, serum AAs levels were measured using the Trace GC 1310 gas chromatography system coupled with the TSQ 8000 triple quadrupole mass spectrometer (Thermo Scientific, Austin, TX, USA) followed by silylation with the BSTFA + 1% TMCS derivatization method. Biochemical parameters, including total cholesterol, HDL-C, LDL-C, triglycerides, fasting glucose, HbA1c, and Creatinine, were assessed for each participant. Trained professionals conducted anthropometric and physical examinations (which included taking blood pressure and heart rate measurements) and family history collection. Results: A total of 112 Kazakh individuals with prediabetes and 55 without prediabetes, aged 36–65 years, were included in the study. Only Alanine and valine showed a significant association with prediabetes risk among the 13 AAs analyzed. Our findings revealed an inverse relationship between Alanine and Valine and prediabetes in individuals of Kazakh ethnicity. Conclusion: A lower serum level of Alanine and Valine may serve as a predictive biomarker for prediabetes in the Kazakh population. Full article

In 1971, chemists from Hoffmann-La Roche and Schering AG independently discovered a new asymmetric intramolecular aldol reaction catalyzed by the natural amino acid proline, a transformation now known as the Hajos–Parrish–Eder–Sauer–Wiechert reaction. These remarkable results remained forgotten until List and Barbas reported in 2000 that L-proline was also able to catalyze intermolecular aldol reactions with non-negligible enantioselectivities. In the same year, MacMillan reported on asymmetric Diels–Alder cycloadditions which were efficiently catalyzed by imidazolidinones deriving from natural amino acids. These two seminal reports marked the birth of modern asymmetric organocatalysis. A further important breakthrough in this field happened in 2005, when Jørgensen and Hayashi independently proposed the use of diarylprolinol silyl ethers for the asymmetric functionalization of aldehydes. During the last 20 years, asymmetric organocatalysis has emerged as a very powerful tool for the facile construction of complex molecular architectures. Along the way, a deeper knowledge of organocatalytic reaction mechanisms has been acquired, allowing for the fine-tuning of the structures of privileged catalysts or proposing completely new molecular entities that are able to efficiently catalyze these transformations. This review highlights the most recent advances in the asymmetric synthesis of organocatalysts deriving from or related to proline, starting from 2008. Full article

Lactic acid (LA) fermentation of dog’s mercury (M. perennis L.) herbal parts was investigated in samples inoculated with either Lactobacteria (Lactobacillus plantarum and Pediococcus pentosaceus, LBF) or whey (WF). Depending on fermentation time, LA concentrations were monitored in a range of 3.4–15.6 g/L with a concomitant pH decline from 6.5 to 3.9. A broad spectrum of cinnamic acids depsides containing glucaric, malic and 2-hydroxyglutaric acids along with quercetin and kaempferol glycosides were detected by LC-DAD-ESI-MSⁿ. Moreover, in this study novel constituents were also found both in unfermented and fermented extracts. Furthermore, amino acids and particular Lactobacteria metabolites such as biogenic amines (e.g., putrescine, 4-aminobutyric acid, cadaverine) and 5-oxoproline were assigned in WF extracts by GC-MS analysis after silylation. Enhanced NFκB and cytokine expression (IL-6, TNFα, IL-8 and IL-1β) was induced by all extracts, both non-fermented and fermented, in NFκB-THP-1 reporter cells, showing a concentration-dependent immunostimulatory effect. The WF extracts were tested for micronuclei formation in THP-1 cells and toxicity in luminescent bacteria (V. fischeri), whereby no mutagenic or toxic effects could be detected, which corroborates their safe use in pharmaceutical remedies. Full article

Cucurbitaceae comprises 800 species, the majority of which are known for their nutritive, economic, and health-promoting effects. This study aims at the metabolome profiling of cucumber (Cucumis sativus) and bottle gourd (Lagenaria siceraria) fruits in a comparative manner for the first time, considering that both species are reported to exhibit several in-common phytochemical classes and bioactivities. Nevertheless, bottle gourd is far less known and/or consumed than cucumber, which is famous worldwide. A multiplex approach, including HR-UPLC/MS/MS, GNPS networking, SPME, and GC/MS, was employed to profile primary and secondary metabolites in both species that could mediate for new health and nutritive aspects, in addition to their aroma profiling, which affects the consumers’ preferences. Spectroscopic datasets were analyzed using multivariate data analyses (PCA and OPLS) for assigning biomarkers that distinguish each fruit. Herein, 107 metabolites were annotated in cucumber and bottle gourd fruits via HR-UPLC/MS/MS analysis in both modes, aided by GNPS networking. Metabolites belong to amino acids, organic acids, cinnamates, alkaloids, flavonoids, pterocarpans, alkyl glycosides, sesquiterpenes, saponins, lignans, fatty acids/amides, and lysophospholipids, including several first-time reported metabolites and classes in Cucurbitaceae. Aroma profiling detected 93 volatiles presented at comparable levels in both species, from which it can be inferred that bottle gourds possess a consumer-pleasant aroma, although data analyses detected further enrichment of bottle gourd with ketones and esters versus aldehydes in cucumber. GC/MS analysis of silylated compounds detected 49 peaks in both species, including alcohols, amino acids, fatty acids/esters, nitrogenous compounds, organic acids, phenolic acids, steroids, and sugars, from which data analyses recognized that the bottle gourd was further enriched with fatty acids in contrast to higher sugar levels in cucumber. This study provides new possible attributes for both species in nutrition and health-care fields based on the newly detected metabolites, and further highlights the potential of the less famous fruit “bottle gourd”, recommending its propagation. Full article

Isotopic analyses of plant samples are now of considerable importance for food certification and plant physiology. In fact, the natural nitrogen isotope composition (δ¹⁵N) is extremely useful to examine metabolic pathways of N nutrition involving isotope fractionations. However, δ¹⁵N analysis of amino acids is not straightforward and involves specific derivatization procedures to yield volatile derivatives that can be analysed by gas chromatography coupled to isotope ratio mass spectrometry (GC-C-IRMS). Derivatizations other than trimethylsilylation are commonly used since they are believed to be more reliable and accurate. Their major drawback is that they are not associated with metabolite databases allowing identification of derivatives and by-products. Here, we revisit the potential of trimethylsilylated derivatives via concurrent analysis of δ¹⁵N and exact mass GC-MS of plant seed protein samples, allowing facile identification of derivatives using a database used for metabolomics. When multiple silylated derivatives of several amino acids are accounted for, there is a good agreement between theoretical and observed N mole fractions, and δ¹⁵N values are satisfactory, with little fractionation during derivatization. Overall, this technique may be suitable for compound-specific δ¹⁵N analysis, with pros and cons. Full article

In this report, a synthetic protocol for the preparation of phosphinic dipeptides of type 5 is presented. These compounds serve as valuable building blocks for the development of highly potent phosphinopeptidic inhibitors of medicinally relevant Zn-metalloproteases and aspartyl proteases. The proposed method is based on the tandem esterification of α-aminophosphinic and acrylic acids under silylating conditions in order to subsequently participate in a P-Michael reaction. The scope of the transformation was investigated by using a diverse set of readily available acrylic acids and (R)-α-aminophosphinic acids, and high yields were achieved in all cases. In most examples reported herein, the isolation of biologically relevant (R,S)-diastereoisomers became possible by simple crystallization from the crude products, thus enhancing the operational simplicity of the proposed method. Finally, functional groups corresponding to acidic or basic natural amino acids are also compatible with the reaction conditions. Based on the above, we expect that the practicality of the proposed protocol will facilitate the discovery of pharmacologically useful bioactive phosphinic peptides. Full article

Ordered mesoporous materials and their modification with multiple functional groups are of wide scientific interest for many applications involving interaction with biological systems and biomolecules (e.g., catalysis, separation, sensor design, nano-science or drug delivery). In particular, the immobilization of enzymes onto solid supports is highly attractive for industry and synthetic chemistry, as it allows the development of stable and cheap biocatalysts. In this context, we developed novel silylated amino acid derivatives (Si-AA-NH₂) that have been immobilized onto SBA-15 materials in biocompatible conditions avoiding the use of toxic catalyst, solvents or reagents. The resulting amino acid-functionalized materials (SBA-15@AA) were characterized by XRD, TGA, EA, Zeta potential, nitrogen sorption and FT-IR. Differences of the physical properties (e.g., charges) were observed while the structural ones remained unchanged. The adsorption of the enzyme lysozyme (Lyz) onto the resulting functionalized SBA-15@AA materials was evaluated at different pHs. The presence of different functional groups compared with bare SBA-15 showed better adsorption results, for example, 79.6 nmol of Lyz adsorbed per m² of SBA-15@Tyr compared with the 44.9 nmol/m² of the bare SBA-15. Full article

Up to now, the taxonomic conflict of the Apocynaceae family has attracted the attention of scientists and researchers worldwide. Recently, this family was divided into five subfamilies. The present study aims to investigate the implication of interlacing macro-, micro-morphological, anatomical, and chemical characteristics of the leaves of eight Apocynaceae plants (Adenium obesum, Dipladenia boliviensis, Carissacarandas, Nerium oleander, Asclepias curassavica, Calotropisprocera, Acokanthera oblongifolia, and Thevetia neriifolia), and to provide valuable taxonomic differentiation of these species. The macro-morphological investigation includes shape, apex, base, and venation of leaves, while the micro-morphological study includes leaf epidermal cells, stomata, and trichomes. The anatomical features of the leaf blade were studied by scanning electron microscope (SEM). Additionally, the chemical composition of the silylated methanolic extract was analyzed by Gas chromatography–mass spectroscopy (GC-MS). Sixty-three compounds were characterized from the silylated extracts of the eight plants, where quinic acid, sucrose, D-pinitol, and D-(−)-fructopyranose were determined as major compounds. The Principal Component Analysis (PCA) based on the chemical composition revealed a significant chemical correlation among all species with the presence of sugars and amino acids, as well as phenolic acids and iridoid glycosides. The cluster analysis, based on all merged characters, showed that the eight species can be categorized into three clusters. The first cluster comprises A.obesum, A. curassavica, and T. neriifolia, while the second cluster contains D. boliviensis, N. oleander, A. oblongifolia, and C. carandas, and the third cluster consists of C. procera alone. This cluster revealed some similarities to the recent classification of Apocynaceae, while it showed inconsistency regarding A.obesum, C. procera, and N. oleander. Due to the obtained inconsistent data and observed variation among the studied species, further study is recommended for more characterization of these species, based on additional parameters, including molecular characteristics, particularly A.obesum, C. procera, and N. oleander. Full article

Antibody-drug conjugate (ADC) is a novel efficient drug delivery system that has been successfully used in clinical practice, and it has become a research hotspot in the anti-tumor drug field. Acid-cleavable linkers were first used in clinical ADCs, but their structural variety (e.g., hydrazone and carbonate) is still limited, and their stability is usually insufficient. Designing novel acid-cleavable linkers for the conjugation of the popular cytotoxin monomethyl auristatin E (MMAE) has always been a significant topic. In this paper, we generate a novel, silyl ether-based acid-cleavable antibody-MMAE conjugate, which skillfully achieves efficient combination of amino-conjugated MMAE with the acid-triggered silyl ether group by introducing p-hydroxybenzyl alcohol (PHB). The stability, acid-dependence cleavage, effective mechanism, efficacy and safety of the resulting ADC were systematically studied; the results show that it exhibits a significant improvement in stability, while maintaining appropriate efficacy and controlled therapeutic toxicity. This strategy is expected to expand a new type of acid-cleavable linkers for the development of ADCs with highly potent payloads. Full article

Fluorinated nucleosides are very important for increased biological and chemical stability of organ fluorine compounds. Synthesis of (1H)-8-trifluloromethyl-2-methyl-4-quinazolinone 3 from 2-amino-3-(trifluoromethyl) benzoic acid 1 was performed. Ribosylation of compound 4 with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose 5 using the silylation method created the benzoylated nucleoside derivative 6. Debenzoylation of the protected nucleoside 6 via reaction with sodium metal in dry methanol to create the corresponding free nucleoside 1,3-bis-(2,3,5-tri-O-benzoyl-β-d-ribofuranosyl)-8-(trifluoromethyl)-2-methyl-4-quinazolinone 7. The structures of the newly synthesis compounds have been confirmed on the basis of IR, ¹HNMR, ¹³CNMR, and mass spectral data. Full article

Gas chromatography–mass spectrometry (GC-MS) is a widely used analytical technique in metabolomics. GC provides the highest resolution of any standard chromatographic separation method, and with modern instrumentation, retention times are very consistent between analyses. Electron impact ionization and fragmentation is generally reproducible between instruments and extensive libraries of spectra are available that enhance the identification of analytes. The major limitation is the restriction to volatile analytes, and hence the requirement to convert many metabolites to volatile derivatives through chemical derivatization. Here we compared the analytical performance of two derivatization techniques, silylation (TMS) and alkylation (MCF), used for the analysis of amino and non-amino organic acids as well as nucleotides in microbial-derived samples. The widely used TMS derivatization method showed poorer reproducibility and instability during chromatographic runs while the MCF derivatives presented better analytical performance. Therefore, alkylation (MCF) derivatization seems to be preferable for the analysis of polyfunctional amines, nucleotides and organic acids in microbial metabolomics studies. Full article