385 research outputs found
Synthesis and biological evaluation of a novel Amadori compound
No full textHere, we report the synthesis, purification, ESI MS and NMR characterization, as well as the SEM analysis of a fructosyl thiophenyl-substituted triazolyl-thione l-alanine (denominated Fru-l-TTA). This novel fructosyl derivative was obtained by solution synthesis using the Amadori reaction, in analogy to other natural fructosyl-amino acids, and fully characterized. In particular, we report an accurate NMR/MS/SEM characterization of Fru-l-TTA alongside some biological properties, and investigated to compare the properties of the artificial derivative of this work with the natural counterparts. In particular, Fru-l-TTA shares with natural fructosyl-amino acids the possibility to inhibit the colony formation of prostate cancer cells and additionally decreases their migration
Lac-l-TTA, a novel lactose-based amino acid–sugar conjugate for anti-metastatic applications
No full textAbstract: Here we describe the synthesis, chromatographic purification, MS and NMR characterization of a new lactosyl-derivative, i.e. a lactosyl thiophenyl-substituted triazolyl-thione l-alanine (Lac-L-TTA). This amino acid–sugar conjugate was prepared by solution synthesis in analogy to the natural fructosyl-amino acids. Furthermore, we investigated the inhibition of PC-3 prostate cancer cell colony formation by this lactose derivative in comparison with the less polar fructose-based derivative, Fru-L-TTA. This let us to compare the properties of the artificial derivative, object of the present work, with the monosaccharide-based counterpart and to obtain a preliminary information on the influence of polarity on such biological activity. A significantly higher anticancer effect of Lac-L-TTA with respect to the fructose analogue emerged from our study suggesting that the anti-metastatic potential of fructosyl-amino acids can be enhanced by increasing the polarity of the compounds, for example by introducing disaccharide moieties in place of fructose
Thiophenyl-substituted triazolyl-thione l-alanine: asymmetric synthesis, aggregation and biological properties
No full textIn this work, we report the asymmetric synthesis and characterization of an artificial amino acid based on triazolyl-thione L-alanine, which was modified with a thiophenyl-substituted moiety, as well as in vitro studies of its nucleic acid-binding ability. We found, by dynamic light scattering studies, that the synthetic amino acid was able to form supramolecular aggregates having a hydrodynamic diameter higher than 200 nm. Furthermore, we demonstrated, by UV and CD experiments, that the heteroaromatic amino acid, whose enzymatic stability was demonstrated by HPLC analysis also after 24 h of incubation in human serum, was able to bind a RNA complex, which is a feature of biomedical interest in view of innovative antiviral strategies based on modulation of RNA-RNA molecular recognition
Reconstructing Bronze Age Armenian Ancestry from Ancient DNA in the South Caucasus: Preliminary Data
No full textPoetics of the same: a philosophical poetic recourse into sameness
No full textPhDThis study endeavours to investigate the philosophical and poetological
dimensions, the philological origins, and significant philosophical-literary
representations of the Same. It also assesses sameness as a philosophical and
poetological modus operandi; that is to say, it analyzes the ways in which the
Same operates in different types of discourses both as an object of investigation
and as an agent of (poetic) thought. The concept of the Same or the operation of
sameness as the philosophical question par excellence will be considered in the
development of Continental philosophy and philosophical poetics from classical
antiquity to Postmodernism, and its transposition into poetry.
The elaboration of the issue of sameness encompasses any philosophical
inquiry which seeks to establish the essence of Being and make it susceptible to a
general, unifying principle: as a search for an underlying element; for a
metaphysical unity or universal, preceding division or difference and amounting
to the harmony in the Universe; or for a transcendental absolute totality.
Postulations of the pure conceptual difference are likewise examined as part of the
elaboration of sameness, and will be viewed as indispensable for revealing the
genuine plenitude of sameness.
Part One traces the inception of sameness as a concept of pure identity,
amounting to the harmony of the Universe by virtue of the operations of
belonging (Presocratics), participation (Plato), and emanation (Plotinus), anchored
in the relationships between the One and the many, between the Whole and its
parts, between the Original and the copy. Part Two inquires into the limits of
postulating sameness in terms of pure identity and points to two possible solutions
to this problem: a philosophical-aesthetic digression from sameness (Kant and
related aesthetic theories of the seventeenth and eighteenth centuries) and the
return to sameness as an absolute totality in Part Three (Schelling and Hegel).
Part Four investigates the re-postulation of sameness as pure Difference
(Nietzsche, Heidegger, Derrida), hence the entire re-organization of thought in
terms of the other. Part Five analyzes the transposition of sameness from
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philosophy into the poetic language of repetition, using Rilke’s Sonnets to
Orpheus as its prime poetic example.
It will be argued that the philosophical displacement of the Same from a
concept of identity into that of difference does not amount to an abandonment of
its plenitude, but rather points to the need for a precarious balance between
sameness and difference, the simultaneous quest for unity and the absolute
singularity of the other. This balance, it will be argued, must be sought for in
every genuine creation
BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study
No full textThis study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to the low micrometric size range. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in the secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. In more detail, the dimer formation achieved by molecular self-docking showed two distinct poses, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior
Biological macromolecule binding and anticancer activity of synthetic alkyne-containing l-phenylalanine derivatives
No full textHerein, we described the synthesis of two l-phenylalanines α-derivatized with a terminal alkyne moiety whose structures differed by phenyl ring halogen substitution (two o-Cl in 1 vs. one p-Br in 2) and investigated their effect on biological macromolecules and living cells. We explored their interaction with quadruplex DNA (G4 DNA), using tel26 and c-myc as models, and bovine serum albumin (BSA). By CD spectroscopy, we found that 1 caused minor tel26 secondary structure changes, leading also to a slight thermal stabilization of this hybrid antiparallel/parallel G4 structure, while the c-myc parallel topology remained essentially unchanged upon 1 binding. Other CD evidences showed the ability of 1 to bind BSA, while molecular docking studies suggested that the same molecule could be housed into the hydrophobic cavity between sub-domains IIA, IIB, and IIIA of the protein. Furthermore, preliminary aggregation studies, based on concentration-dependent spectroscopic experiments, suggested the ability of 1 to aggregate forming noncovalent polymeric systems in aqueous solution. Differently from 1, the bromine-modified compound was able to bind Cu(II) ion, likely with the formation of a CuL2 complex, as found by UV spectroscopy. Finally, cell tests excluded any cytotoxic effect of both compounds toward normal cells, but showed slight antiproliferative effects of 2 on PC3 cancerous cells at 24 h, and of 1 on both T98G and MDA-MB-231 cancer cells at 48 h
Screening study of TUBB4A in isolated dystonia
No full textMutations in TUBB4A have been identified to cause a wide phenotypic spectrum ranging from hereditary generalized dystonia with whispering dysphonia (DYT4) to the leukodystrophy hypomyelination syndrome with atrophy of the basal ganglia and cerebellum (H-ABC). To test for the contribution of TUBB4A mutations in different ethnicities (Spanish, Italian, Korean, Japanese), we screened 492 isolated dystonia cases for mutations in this gene and for the first time determined TUBB4A copy number variations in 336 dystonia patients. A potentially pathogenic rare 3bp-in-frame deletion was found in a patient with cervical dystonia but no copy number variations were detected in this study, suggesting that TUBB4A mutations exceedingly rarely contribute to the etiology of isolated dystonia
Superoxide-producing lipoprotein fraction from Stevia leaves: definition of specific activity
No full textAbstract Background Stevia rebaudiana Bertoni has various pharmacological actions, which includes antidiabetic, antioxidant, anti-inflammatory activities. The superoxide and consequently NADPH oxidase (Nox) are relevant targets involved in biological effects of Stevia. The presence of NADPH-containing superoxide-producing lipoprotein (suprol) in Stevia leaves has not yet been tested. The mechanism of producing superoxide radicals (O2 −) by suprol was determined in vitro, which is associated with the electron transfer from NADPH in the composition of suprol by traces of transition metal ions (Fe3+ or Cu2+) to molecular oxygen, turning it into O2 −. It is expected that the therapeutic efficacy of Stevia leaves is caused by specific activity of superoxide-producing lipoprotein fraction. Methods For the first time, from the dry leaves of Stevia the NADPH-containing superoxide-producing lipoprotein was isolated and purified. The specific content of suprol (milligrams in 1 g of Stevia leaves- mg/g) was determined after desalination of suprol and lyophilization. Results According to the method provided, the specific content of the isolated suprol from Stevia’s leaves was up to 4.5 ± 0.2 mg / g (yields up to 68.5 ± 4.7%, p < 0.05, n = 6). Nox forms a stable complex with suprol. The optical absorption spectrum of the Nox-suprol complex represents the overlapping suprol and Nox spectra, with a certain background increase and characteristic features of optical absorption for Nox. Due to O2 − producing capacity suprol-Nox complex discolors KMnO4 solutions, Coomassie brilliant blue, restores nitrotetrazolium blue to formazan and oxidizes epinephrine to adrenochrome. The oxidation activity of adrenaline is 50.3 ± 5.1 U / mg / ml (p < 0.05, n = 6). Conclusion Superoxide-producing lipoprotein fraction-Nox complex from Stevia leaves (membranes) can modulate redox regulated signaling pathways and may play a positive role in type-2 diabetes by means of adrenaline oxidation mechanism
Utilization of Cassava Wastes for Value Added Products: An Overview
No full textDifferent categories of wastes and residues generated during cassava processing must be properly managed so as not to constitute environmental hazard. The huge cost of treatment and disposal create avenue for alternative uses to be explored. This study reviewed the various value added products which can be produced from cassava wastes substrate as feed-stock for bio-energy. Theoretically, it was estimated that one kilogram of cassava peelings will yield 118 g of bio-methane and 226 g of bio-ethanol, one liter of cassava wastewater will yield 16 g and 9 g of bio-ethanol and bio-methane, respectively. Whereas 20 g and 10 g of bio-ethanol and bio-methane, respectively will be obtained from one liter of bagasse. These was also compared with the estimated values obtained based on Chemical Oxygen Demand (COD): 23.9 g of CH4/g COD in one liter of cassava wastewater, Volatile Solids (VS): 23.1 g of CH4/g VS in one liter of cassava wastewater and Total Solids (TS):22.9g of CH4/g TS in one liter of cassava wastewater and 0.414 g using Buswell’s equation. This is study can be utilized when making decision on the potentials of cassava wastes for value added products
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