The antioxidant activity of Scorzonera parviflora Jacq. roots were assessed by measuring their ability to scavenge ABTS and DPPH radicals. Bioactivity-guided fractionation was utilized to identify the compound(s) responsible for this activity. The most active phase, ethyl acetate, was isolated using column chromatography. The resulting fractions were then purified using preparative TLC on reverse phase and semi-preparative HPLC. The structures of the pure compounds were elucidated by spectral analysis (MS and 1H, 13C, 2D-NMR). Three undescribed phenolic acid derivatives, namely parvifloric acid A (1), B (2), and C (3), and one new sesquiterpene lactone, parviflorin (4) together with seven known compounds were isolated and identified as scopolin (5), scopoletin (6), caffeic acid (7), protocatechuic acid (8), 4,5-O-dicaffeoylquinic acid (9) 3,5-O-dicaffeoylquinic acid (10), and 3,5-O-dicaffeoylquinic acid methyl ester (11). Finally, the pure compounds obtained were tested to evaluate their antioxidant capacities, using ABTS and DPPH radical scavenging potencies. The highest activity was observed with 3,5-O-dicaffeoylquinic acid (10), followed by its methyl ester.
- Klíčová slova
- Antioxidant activity, Asteraceae, Phenolic acids, Scorzonera parviflora, Sesquiterpene lactone,
- MeSH
- antioxidancia * farmakologie izolace a purifikace chemie MeSH
- fytonutrienty farmakologie izolace a purifikace MeSH
- hydroxybenzoáty * izolace a purifikace farmakologie chemie MeSH
- kořeny rostlin * chemie MeSH
- molekulární struktura MeSH
- Scorzonera * chemie MeSH
- seskviterpeny farmakologie izolace a purifikace chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia * MeSH
- fytonutrienty MeSH
- hydroxybenzoáty * MeSH
- phenolic acid MeSH Prohlížeč
- seskviterpeny MeSH
Preptin, a 34-amino acid peptide derived from pro-IGF2, is believed to influence various physiological processes, including insulin secretion and the regulation of bone metabolism. Despite its recognized involvement, the precise physiological role of preptin remains enigmatic. To address this knowledge gap, we synthesized 16 analogs of preptin, spanning a spectrum from full-length forms to fragments, and conducted comprehensive comparative activity evaluations alongside native human, mouse and rat preptin. Our study aimed to elucidate the physiological role of preptin. Contrary to previous indications of broad biological activity, our thorough analyses across diverse cell types revealed no significant biological activity associated with preptin or its analogs. This suggests that the associations of preptin with various diseases or tissue-specific abundance fluctuations may be influenced by factors beyond preptin itself, such as higher levels of IGF2 or IGF2 proforms present in tissues. In conclusion, our findings challenge the conventional notion of preptin as an isolated biologically active molecule and underscore the complexity of its interactions within biological systems. Rather than acting independently, the observed effects of preptin may arise from experimental conditions, elevated preptin concentrations, or interactions with related molecules such as IGF2.
- MeSH
- insulinu podobný růstový faktor II * metabolismus MeSH
- inzulin metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- myši MeSH
- peptidové fragmenty metabolismus MeSH
- proteinové prekurzory metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- IGF2 protein, human MeSH Prohlížeč
- insulinu podobný růstový faktor II * MeSH
- inzulin MeSH
- peptidové fragmenty MeSH
- preptin MeSH Prohlížeč
- proteinové prekurzory MeSH
Helicenes are very attractive chiral non-planar polycyclic aromatic hydrocarbons possessing strong chiroptical properties. However, most of the helicenes absorb light mainly in the ultraviolet region, with only a small segment in the blue part of the visible spectrum. Furthermore, carbo[n]helicenes exhibit only weak luminescence that limits their utilization. Herein, we demonstrate that peripheral decoration of the helicene backbone with an aryl-carbonyl group shifts the absorption to the visible region and simultaneously improves their fluorescence quantum yields. We thus show that the carbonyl group, commonly considered as detrimental to emission, has the capability of improving optical and photophysical properties. Two different families, aceno[n]helicenones and fluoreno[n]helicenes, are presented with comprehensive spectrochemical characterization. TD-DFT calculations were implemented to clarify their electronic profiles. We show that increasing the helical length in aceno[n]helicenes increases absorption onset, g abs and g lum. Extension of the peripheral aromatic part in fluoreno[n]helicenes leads to a blue shift in both absorption and emission.
- Publikační typ
- časopisecké články MeSH
Cyclic dinucleotides (CDNs) are important second messengers in bacteria and eukaryotes. Detailed characterization of their physicochemical properties is a prerequisite for understanding their biological functions. Herein, we examine acid-base and electromigration properties of selected CDNs employing capillary electrophoresis (CE), density functional theory (DFT), and nuclear magnetic resonance (NMR) spectroscopy to provide benchmark pKa values, as well as to unambiguously determine the protonation sites. Acidity constants (pKa) of the NH+ moieties of adenine and guanine bases and actual and limiting ionic mobilities of CDNs were determined by nonlinear regression analysis of the pH dependence of their effective electrophoretic mobilities measured by CE in aqueous background electrolytes in a wide pH range (0.98-11.48), at constant temperature (25°C), and constant ionic strength (25 mM). The thermodynamic pKa values were found to be in the range 3.31-4.56 for adenine and 2.28-3.61 for guanine bases, whereas the pKa of enol group of guanine base was in the range 10.21-10.40. Except for systematic shifts of ∼2 pKa, the pKa values calculated by the DFT-D3//COSMO-RS composite protocol that included large-scale conformational sampling and "cross-morphing" were in a relatively good agreement with the pKas determined by CE and predict N1 atom of adenine and N7 atom of guanine as the protonation sites. The protonation of the N1 atom of adenine and N7 atom of guanine in acidic background electrolytes (BGEs) and the dissociation of the enol group of guanine in alkaline BGEs was confirmed also by NMR spectroscopy.
- Klíčová slova
- DFT calculations, NMR spectroscopy, acidity constant, capillary electrophoresis, cyclic dinucleotides,
- MeSH
- dinukleosidfosfáty chemie MeSH
- elektroforéza kapilární * metody MeSH
- koncentrace vodíkových iontů MeSH
- magnetická rezonanční spektroskopie * metody MeSH
- protony * MeSH
- teorie funkcionálu hustoty MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dinukleosidfosfáty MeSH
- protony * MeSH
Cyclic dinucleotides (CDNs) trigger the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which plays a key role in cytosolic DNA sensing and thus in immunomodulation against infections, cell damage and cancer. However, cancer immunotherapy trials with CDNs have shown immune activation, but not complete tumor regression. Nevertheless, we designed a novel class of CDNs containing vinylphosphonate based on a STING-affinity screening assay. In vitro, acyloxymethyl phosphate/phosphonate prodrugs of these vinylphosphonate CDNs were up to 1000-fold more potent than the clinical candidate ADU-S100. In vivo, the lead prodrug induced tumor-specific T cell priming and facilitated tumor regression in the 4T1 syngeneic mouse model of breast cancer. Moreover, we solved the crystal structure of this ligand bound to the STING protein. Therefore, our findings not only validate the therapeutic potential of vinylphosphonate CDNs but also open up opportunities for drug development in cancer immunotherapy bridging innate and adaptive immunity.
- Klíčová slova
- Cancer, Cyclic dinucleotides, Immunotherapy, Intratumoral administration, STING,
- MeSH
- DNA MeSH
- imunoterapie MeSH
- myši MeSH
- nádory * farmakoterapie MeSH
- nukleotidy cyklické * farmakologie metabolismus MeSH
- přirozená imunita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ADU-S100 MeSH Prohlížeč
- DNA MeSH
- nukleotidy cyklické * MeSH
Insulin is a peptide responsible for regulating the metabolic homeostasis of the organism; it elicits its effects through binding to the transmembrane insulin receptor (IR). Insulin mimetics with agonistic or antagonistic effects toward the receptor are an exciting field of research and could find applications in treating diabetes or malignant diseases. We prepared five variants of a previously reported 20-amino acid insulin-mimicking peptide. These peptides differ from each other by the structure of the covalent bridge connecting positions 11 and 18. In addition to the peptide with a disulfide bridge, a derivative with a dicarba bridge and three derivatives with a 1,2,3-triazole differing from each other by the presence of sulfur or oxygen in their staples were prepared. The strongest binding to IR was exhibited by the peptide with a disulfide bridge. All other derivatives only weakly bound to IR, and a relationship between increasing bridge length and lower binding affinity can be inferred. Despite their nanomolar affinities, none of the prepared peptide mimetics was able to activate the insulin receptor even at high concentrations, but all mimetics were able to inhibit insulin-induced receptor activation. However, the receptor remained approximately 30% active even at the highest concentration of the agents; thus, the agents behave as partial antagonists. An interesting observation is that these mimetic peptides do not antagonize insulin action in proportion to their binding affinities. The compounds characterized in this study show that it is possible to modulate the functional properties of insulin receptor peptide ligands using disulfide mimetics.
- Klíčová slova
- antagonism, dicarba, disulfide mimetics, insulin mimetic peptide, insulin receptor, staple, triazole,
- MeSH
- disulfidy chemie MeSH
- inzulin * metabolismus MeSH
- peptidy chemie MeSH
- receptor inzulinu * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- disulfidy MeSH
- inzulin * MeSH
- peptidy MeSH
- receptor inzulinu * MeSH
Aliphatic hydrocarbons (HCs) are usually analyzed by gas chromatography (GC) or matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. However, analyzing long-chain HCs by GC is difficult because of their low volatility and the risk of decomposition at high temperatures. MALDI cannot distinguish between isomeric HCs. An alternative approach based on silver ion high-performance liquid chromatography (Ag-HPLC) is shown here. The separation of HC standards and cuticular HCs was accomplished using two ChromSpher Lipids columns connected in series. A gradient elution of the analytes was optimized using mobile phases prepared from hexane (or isooctane) and acetonitrile, 2-propanol, or toluene. HCs were detected by atmospheric pressure chemical ionization mass spectrometry (APCI-MS). Good separation of the analytes according to the number of double bonds, cis/trans geometry, and position of double bonds was achieved. The retention times increased with the number of double bonds, and trans isomers eluted ahead of cis isomers. The mobile phase significantly affected the mass spectra of HCs. Depending on the mobile phase composition, deprotonated molecules, molecular ions, protonated molecules, and various solvent-related adducts of HCs were observed. The optimized Ag-HPLC/APCI-MS was applied for characterizing cuticular HCs from a flesh fly, Neobellieria bullata, and cockroach, Periplaneta americana. The method made it possible to detect a significantly higher number of HCs than previously reported for GC or MALDI-MS. Unsaturated HCs were frequently detected as isomers differing by double-bond position(s). Minor HCs with trans double bonds were found beside the prevailing cis isomers. Ag-HPLC/APCI-MS has great potential to become a new tool in chemical ecology for studying cuticular HCs.
- Klíčová slova
- Neobellieria bullata, Periplaneta americana, double bonds, hydrocarbons, mass spectrometry, semiochemicals,
- MeSH
- atmosférický tlak MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- stříbro * chemie MeSH
- uhlovodíky * MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- stříbro * MeSH
- uhlovodíky * MeSH
A series of regioisomeric push-pull amino-nitro [6]helicenes and a related [7]helicene derivative were prepared and their racemates resolved into enantiomers. Compared to the parent helicenes, they exhibit red-shifted UV-Vis spectra, pronounced dipole moments, altered chiroptical properties such as remarkable optical rotatory power, and can form nanocrystalline Langmuir-Blodgett films.
- MeSH
- polycyklické sloučeniny * MeSH
- stereoizomerie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- helicenes MeSH Prohlížeč
- polycyklické sloučeniny * MeSH
The synthesis of a tetrathiafulvalene (TTF) derivative, S-[4-({4-[(2,2'-bi-1,3-dithiol-4-ylmethoxy)methyl] phenyl}ethynyl)phenyl] ethanethioate, suitable for the modification of gold nanoparticles (AuNPs), is described in this article. The TTF ligand was self-assembled on the AuNP surface through ligand exchange, starting from dodecanethiol-stabilized AuNPs. The resulting modified AuNPs were characterized by TEM, UV-Vis spectroscopy, and electrochemistry. The most suitable electrochemical method was the phase-sensitive AC voltammetry at very low frequencies of the sine-wave perturbation. The results indicate a diminishing electronic communication between the two equivalent redox centers of TTF and also intermolecular donor-acceptor interactions manifested by an additional oxidation wave upon attachment of the ligand to AuNPs.
- Klíčová slova
- AC voltammetry, TEM, gold nanoparticles, spectroscopy, synthesis, tetrathiafulvalene,
- MeSH
- elektrochemie metody MeSH
- kovové nanočástice * chemie MeSH
- ligandy MeSH
- zlato * chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ligandy MeSH
- tetrathiafulvalene MeSH Prohlížeč
- zlato * MeSH
Cyclic dinucleotides (CDNs) are second messengers that activate stimulator of interferon genes (STING). The cGAS-STING pathway plays a promising role in cancer immunotherapy. Here, we describe the synthesis of CDNs containing 7-substituted 7-deazapurine moiety. We used mouse cyclic GMP-AMP synthase and bacterial dinucleotide synthases for the enzymatic synthesis of CDNs. Alternatively, 7-(het)aryl 7-deazapurine CDNs were prepared by Suzuki-Miyaura cross-couplings. New CDNs were tested in biochemical and cell-based assays for their affinity to human STING. Eight CDNs showed better activity than 2'3'-cGAMP, the natural ligand of STING. The effect on cytokine and chemokine induction was also evaluated. The best activities were observed for CDNs bearing large aromatic substituents that point above the CDN molecule. We solved four X-ray structures of complexes of new CDNs with human STING. We observed π-π stacking interactions between the aromatic substituents and Tyr240 that are involved in the stabilization of CDN-STING complexes.
- MeSH
- cytokiny MeSH
- interferony MeSH
- lidé MeSH
- ligandy MeSH
- membránové proteiny * metabolismus MeSH
- myši MeSH
- nukleotidy cyklické * chemie MeSH
- nukleotidyltransferasy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 7-deazapurine MeSH Prohlížeč
- cytokiny MeSH
- interferony MeSH
- ligandy MeSH
- membránové proteiny * MeSH
- nukleotidy cyklické * MeSH
- nukleotidyltransferasy MeSH
