PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - Scopus: 6Functional Characterization of a Novel Cyp119 Variant To Explore Its Biocatalytic Potential(John Wiley and Sons Inc, 2022) Sakalli, T.; Surmeli, N.B.Biocatalysts are increasingly applied in the pharmaceutical and chemical industry. Cytochrome P450 enzymes (P450s) are valuable biocatalysts due to their ability to hydroxylate unactivated carbon atoms using molecular oxygen. P450s catalyze reactions using nicotinamide adenine dinucleotide phosphate (NAD(P)H) cofactor and electron transfer proteins. Alternatively, P450s can utilize hydrogen peroxide (H2O2) as an oxidant, but this pathway is inefficient. P450s that show higher efficiency with peroxides are sought after in industrial applications. P450s from thermophilic organisms have more potential applications as they are stable toward high temperature, high and low pH, and organic solvents. CYP119 is an acidothermophilic P450 from Sulfolobus acidocaldarius. In our previous study, a novel T213R/T214I (double mutant [DM]) variant of CYP119 was obtained by screening a mutant library for higher peroxidation activity utilizing H2O2. Here, we characterized the substrate scope; stability toward peroxides; and temperature and organic solvent tolerance of DM CYP119 to identify its potential as an industrial biocatalyst. DM CYP119 displayed higher stability than wild-type (WT) CYP119 toward organic peroxides. It shows higher peroxidation activity for non-natural substrates and higher affinity for progesterone and other bioactive potential substrates compared to WT CYP119. DM CYP119 emerges as a new biocatalyst with a wide range of potential applications in the pharmaceutical and chemical industry. © 2021 International Union of Biochemistry and Molecular Biology, Inc.Article Citation - Scopus: 4Quasi-Supervised Strategies for Compound-Protein Interaction Prediction(John Wiley and Sons Inc, 2022) Çakı, O.; Karaçalı, B.In-silico compound-protein interaction prediction addresses prioritization of drug candidates for experimental biochemical validation because the wet-lab experiments are time-consuming, laborious and costly. Most machine learning methods proposed to that end approach this problem with supervised learning strategies in which known interactions are labeled as positive and the rest are labeled as negative. However, treating all unknown interactions as negative instances may lead to inaccuracies in real practice since some of the unknown interactions are bound to be positive interactions waiting to be identified as such. In this study, we propose to address this problem using the Quasi-Supervised Learning (QSL) algorithm. In this framework, potential interactions are predicted by estimating the overlap between a true positive dataset of compound-protein pairs with known interactions and an unknown dataset of all the remaining compound-protein pairs. The potential interactions are then identified as those in the unknown dataset that overlap with the interacting pairs in the true positive dataset in terms of the associated similarity structure. We also address the class-imbalance problem by modifying the conventional cost function of the QSL algorithm. Experimental results on GPCR and Nuclear Receptor datasets show that the proposed method can identify actual interactions from all possible combinations. © 2021 Wiley-VCH GmbH.Article Citation - Scopus: 10Use of Magic Sandwich Echo and Fast Field Cycling Nmr Relaxometry on Honey Adulteration With Corn Syrup(John Wiley and Sons Ltd, 2022) Berk, B.; Cavdaroglu, C.; Grunin, L.; Ardelean, I.; Kruk, D.; Mazi, B.G.; Oztop, M.H.BACKGROUND: Adulteration is defined as the intentional addition of a material that is not a part of the nature. In this study, a non-conventional time domain nuclear magnetic resonance (TD-NMR) pulse sequence: magic sandwich echo (MSE) was used to detect the adulteration of honey by glucose syrup (GS) and high fructose corn syrup (HFCS) accompanied with T1 and T2 relaxation times. Also, fast field cycling NMR (FFC-NMR) relaxometry and multivariate analysis were performed to investigate the adulteration. RESULTS: Higher maltose in GS and changing glucose to water ratio of HFCS gave high correlation with the crystal content values. In HFCS adulteration, two separate populations of protons having different T2 values were detected and T1 times were also used to determine GS adulteration. Addition of GS increased T1 while addition of HFCS increased T2, significantly. CONCLUSION: The results showed that it is possible to differentiate the unadulterated and adulterated honey samples by using TD-NMR relaxation times and crystal content values obtained by the MSE sequence. By FFC-NMR relaxometry, not only GS addition but also the amount of GS was examined. The multivariate analysis technique of principal component analysis was able to distinguish the types of adulterants. © 2021 Society of Chemical Industry. © 2021 Society of Chemical Industry.Article Citation - Scopus: 13Her2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual Ph-Sensitive Dox Release(John Wiley and Sons Inc, 2022) Bayram, N.N.; Ulu, G.T.; Topuzoğulları, M.; Baran, Y.; Dinçer, İşoğlu, S.Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition−fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide–doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery. © 2021 Wiley-VCH GmbHArticle Citation - Scopus: 4Comparative Proteomic Analysis of Leishmania Parasites Isolated From Visceral and Cutaneous Leishmaniasis Patients(Cambridge University Press, 2022) Dinç, M.; Yalçln, T.; Çavuş, I.; Özbilgin, A.Leishmaniasis is an infectious disease in which different clinical manifestations are classified into three primary forms: visceral, cutaneous and mucocutaneous. These disease forms are associated with parasite species of the protozoan genus Leishmania. For instance, Leishmania infantum and Leishmania tropica are typically linked with visceral (VL) and cutaneous (CL) leishmaniasis, respectively; however, these two species can also cause other form to a lesser extent. What is more alarming is this characteristic, which threatens current medical diagnosis and treatment, is started to be acquired by other species. Our purpose was to address this issue; therefore, gel-based and gel-free proteomic analyses were carried out on the species L. infantum to determine the proteins differentiating between the parasites caused VL and CL. In addition, L. tropica parasites representing the typical cases for CL were included. According to our results, electrophoresis gels of parasites caused to VL were distinguishable regarding the repetitive down-regulation on some specific locations. In addition, a distinct spot of an antioxidant enzyme, superoxide dismutase, was shown up only on the gels of CL samples regardless of the species. In the gel-free approach, 37 proteins that were verified with a second database search using a different search engine, were recognized from the comparison between VL and CL samples. Among them, 31 proteins for the CL group and six proteins for the VL group were determined differentially abundant. Two proteins from the gel-based analysis, pyruvate kinase and succinyl-coA:3-ketoacid-coenzyme A transferase analysis were encountered in the protein list of the CL group. Copyright © The Author(s), 2021. Published by Cambridge University Press.Article Citation - Scopus: 7High-Pressure Structural Studies and Pressure-Induced Sensitisation of 3,4,5-Trinitro(Royal Society of Chemistry, 2023) Atceken, N.; Hemingway, J.; Bull, C.L.; Liu, X.; Michalchuk, A.A.L.; Konar, S.; Morrison, C.A.Herein we report the first high-pressure study of the energetic material 3,4,5-trinitro-1H-pyrazole (3,4,5-TNP) using neutron powder diffraction and single-crystal X-ray diffraction. A new high-pressure phase, termed Form II, was first identified through a substantial change in the neutron powder diffraction patterns recorded over the range 4.6-5.3 GPa, and was characterised further by compression of a single crystal to 5.3 GPa in a diamond-anvil cell using X-ray diffraction. 3,4,5-TNP was found to be sensitive to initiation under pressure, as demonstrated by its unexpected and violent decomposition at elevated pressures in successive powder diffraction experiments. Initiation coincided with the sluggish phase transition from Form I to Form II. Using a vibrational up-pumping model, its increased sensitivity under pressure can be explained by pressure-induced mode hardening. These findings have potential implications for the safe handling of 3,4,5-TNP, on the basis that shock- or pressure-loading may lead to significantly increased sensitivity to initiation. © 2023 The Royal Society of Chemistry.Article Citation - WoS: 2Citation - Scopus: 2Investigating Influences of Intravenous Fluids on Huvec and U937 Monocyte Cell Lines Using the Magnetic Levitation Method(ROYAL SOC CHEMISTRY, 2023) Keçili, Seren; Kaymaz, Sumeyra Vural; Özoğul, Beyzanur; Tekin, H. Cumhur; Elitaş, MeltemIntravenous fluids are being widely used in patients of all ages for preventing or treating dehydration in the intensive care units, surgeries in the operation rooms, or administering chemotherapeutic drugs at hospitals. Dextrose, Ringer, and NaCl solutions are widely received as intravenous fluids by hospitalized patients. Despite their widespread administration for over 100 years, studies on their influences on different cell types have been very limited. Increasing evidence suggests that treatment outcomes might be altered by the choice of the administered intravenous fluids. In this study, we investigated the influences of intravenous fluids on human endothelial (HUVEC) and monocyte (U937) cell lines using the magnetic levitation technique. Our magnetic levitation platform provides label-free manipulation of single cells without altering their phenotypic or genetic properties. It allows for monitoring and quantifying behavior of single cells by measuring their levitation heights, deformation indices, and areas. Our results indicate that HUVEC and U937 cell lines respond differently to different intravenous fluids. Dextrose solution decreased the viability of both cell lines while increasing the heterogeneity of areas, deformation, and levitation heights of HUVEC cells. We strongly believe that improved outcomes can be achieved when the influences of intravenous fluids on different cell types are revealed using robust, label-free, and efficient methods. Label-free analysis of cells exposed to intravenous fluids can be achieved through magnetic levitation technology coupled with cell-morphology characterization.Article Citation - WoS: 1Citation - Scopus: 2Recycling of Gas-To Sludge as a Potential Organic Amendment: Effect on Soil and Cotton Properties Under Hyperarid Conditions(Academic Press, 2023) Mabrouk, O.; Hamdi, H.; Sayadi, S.; Al-Ghouti, M.A.; Abu-Dieyeh, M.; Kogbara, R.; Al-Sharshani, A.Gas-to-liquid (GTL) sludge is a specific wastewater treatment by-product, which is generated during the industrial process of natural gas conversion to transportation fuels. This least studied sludge is pathogen-free and rich in organic carbon and plant nutrients. Therefore, it can be reused for soil enhancement as a sustainable management strategy to mitigate landfill gas emissions. In this field study, we compared the performance of soil treatments with GTL sludge to the more conventional chemical fertilizers and cow manure compost for the cultivation of cotton under hyperarid conditions. After a complete growing season, GTL sludge application resulted in the enhancement of soil properties and plant growth compared to conventional inputs. As such, there was a significant dose-dependent increase of soil organic matter (4.01% and 4.54%), phosphorus (534 and 1090 mg kg−1), and cumulative lint yield (4.68 and 5.67 t ha−1) for GTL sludge application rates of 1.5% and 3%, respectively. The produced fiber quality was adequate for an upland cotton variety (Gossypium hirsutum var. MAY 344) and appeared more dependent on the prevailing climate conditions than soil treatments. On the other hand, the adverse effects generally related to industrial sludge reuse were not significant and did not affect the designed agro-environmental system. Accordingly, plants grown on GTL sludge-amended soils showed lower antioxidant activity despite significant salinity increase. In addition, the concentrations of detected heavy metals in soil were within the standards’ limits, which did not pose environmental issues under the described experimental conditions. Leachate analysis revealed no risks for groundwater contamination with phytotoxic metals, which were mostly retained by the soil matrix. Therefore, recycling GTL sludge as an organic amendment can be a sustainable solution to improve soil quality and lower carbon footprint. To reduce any environmental concerns, an application rate of 1.5% could be provisionally recommended since a two-fold increase in sludge dose did not result in a significant yield improvement. © 2023 Elsevier LtdArticle Citation - Scopus: 3A Reaction-Based Scenario for Fluorescence Probing of Au(iii) Ions in Human Cells and Plants(Royal Soc Chemistry, 2023) Eren, Merve Cevik; Eren, Ahmet; Dartar, Suay; Kaya, Beraat Umur; Ucuncu, Muhammed; Varlikli, Canan; Emrullahoglu, MustafaA BODIPY-based fluorophore decorated with a gold specific reactive handle (e.g., 2-alkynylallyl alcohol) displayed a ratiometric fluorescence change in response to Au3+ ions with extraordinary selectivity over other competing metal species, including Hg2+, Cu2+, Zn2+ and Pd2+. By way of a gold-catalyzed intramolecular cyclisation-isomerisation reaction sequence, a BODIPY construct with an extended p-conjugation transformed into a new structure with a relatively short p-system. This unique chemical transformation was accompanied by, and resulted in, a dramatic shift in the emission and absorption wavelength, which could be monitored as distinct changes in the color of the solution's emission. Apart from its outstanding analytical performance in solution, including a quick response time (<10 s), unique specificity, a high-fold ratio-metric change (62-fold), and a remarkably low detection limit (358 nM), the probe also proved useful in monitoring Au3+ ions in human cells and plants (e.g., Nicotiana benthamiana).Article Citation - WoS: 3Citation - Scopus: 3Synthesis, Cytotoxicity, and Antibacterial Studies of 2,4,5,6-Substituted Hexahydro-1h(Wiley, 2023) Yetişkin, Egehan; Gündoğdu, Özlem; Mete, Derya; Celebioglu, Neslihan; Kara, Yunus; Şanlı-Mohamed, GulsahIn this study, synthesis of novel isoindole-1,3-dione analogues bearig halo, hydroxy, and acetoxy groups at the position 4,5,6 of the bicyclic imide ring was performed to examine their potential anticancer effects against some cell lines. A multistep chemical pathway was used to synthesize the derivatives. The cytotoxic effect of trisubstituted isoindole derivatives were evaluated by determining cellular viability using the MTT assay against A549, PC-3, HeLa, Caco-2, and MCF-7 cell lines. The C-2 selective ring-opening products were obtained from the ring-opening reaction of 5-alkyl/aryl-2-hydroxyhexahydro-4H-oxireno[2,3-e]isoindole-4,6(5H)-diones with nucleophiles such as chloride (Cl-) and bromide (Br-) ions. In addition, the ring-opening products halodiols were converted to their related acetates. The anticancer activity of synthesized isoindole-1,3-dione derivatives was investigated against HeLa, A549, MCF-7, PC3, and Caco-2 cells in vitro and resulted in varies cytotoxic effect depend on the group attached to the isoindole molecule. Furthermore, the evaluation of the antimicrobial action of trisubstituted isoindole derivatives against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria was assessed and found out selective inhibition of the both bacterial growth via different trisubstituted isoindole derivatives. The results of this work encourage further research on the potential utilization of trisubstituted isoindole derivatives as cytotoxic and antimicrobial agents.