Chemistry / Kimya
Permanent URI for this collectionhttps://hdl.handle.net/11147/4072
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Article Citation - WoS: 2Citation - Scopus: 2Gas Phase Fragmentation Behavior of Proline in Macrocyclic B7 Ions(American Chemical Society, 2023) Taşoğlu, Çağdaş; Arslanoğlu, Alper; Arslanoğlu, Alper; Yalçın, Talat; Yalçın, Talat; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyThefragmentation characteristics of b (7) ionsproduced from proline-containing heptapeptides have been studiedin detail. The study has utilized the following C-terminally amidatedmodel peptides: PA(6), APA(5), A(2)PA(4), A(3)PA(3), A(4)PA(2), A(5)PA, A(6)P, PYAGFLV, PAGFLVY, PGFLVYA, PFLVYAG,PLVYAGF, PVYAGFL, YPAGFLV, YAPGFLV, YAGPFLV, YAGFPLV, YAGFLPV, YAGFLVP,PYAFLVG, PVLFYAG, A(2)PXA(3), and A(2)XPA(3) (where X = C, D, F, G, L, V, and Y, respectively). The resultshave shown that b (7) ions undergo head-to-tailcyclization and form a macrocyclic structure. Under the collision-induceddissociation (CID) condition, it generates nondirect sequence ionsregardless of the position of the proline and the neighboring aminoacid residues. This study highlights the unusual and unique fragmentationbehavior of proline-containing heptapeptides. Following the head-to-tailcyclization, the ring opens up and places the proline residue in theN-terminal position while forming a regular oxazolone form of b (2) ions for all peptide series. Then, the fragmentationreaction pathway is followed by the elimination of proline with itsC-terminal neighbor residue as an oxazolone (e.g., PXoxa) for all proline-containing peptide series.Article Citation - WoS: 4Citation - Scopus: 5Development of Ab3-Type Novel Phthalocyanine and Porphyrin Photosensitizers Conjugated With Triphenylphosphonium for Higher Photodynamic Efficacy(American Chemical Society, 2022) Albakour, Mohamad; Önal, Emel; Akgül, Bünyamin; Erdoğan, İpek; Gümüşgöz Çelik, Gizem; Erdoğan, İpek; Özçelik, Serdar; Tüncel, Özge; Özçelik, Serdar; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyThere are a number of lipophilic cations that can be chosen; the triphenylphosphonium (TPP) ion is particularly unique for mitochondrion targeting, mainly due to its simplicity in structure and ease to be linked to the target molecules. In this work, mitochondrion-targeted AB3-type novel phthalocyanine and porphyrin photosensitizers (PSs) were synthesized and their photophysical photochemical properties were defined. Fluorescence quantum yields (φF) are 0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields (φΔ) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB3TPP-Pc, AB3TPP-Por-C4, and AB3TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated PS cell viabilities of A549 and BEAS-2B lung cells were comparatively measured and IC-50 values were determined. AB3TPP-Por-C4, AB3TPP-Por-C6, and AB3TPP-Pc compounds compared to the reference molecules ZnPc and H2TPP were found to be highly cytotoxic (sub-micromolar concentration) under the light. LuPcPox(OAc) is the most effective molecule regarding cell killing (the activity). The cell killing of the TPP-conjugated porphyrin derivatives exhibits a similar response compared to LuPcPox(OAc) when the light absorbing factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins absorb less light (lower extinction coefficient) but produce more radical species (higher singlet-oxygen quantum yield) and therefore effectively kill the cells. The singlet oxygen-producing capacity of AB3TPP-Pc is almost 3 times higher compared to LuPcPox(OAc) and 50% more efficient with respect to ZnPc, suggesting that TPP-conjugated phthalocyanine may serve as a good photosensitizer for photodynamic therapy (PDT). The high singlet oxygen generation capacity of these novel TPP-conjugated porphyrin and phthalocyanine PS suggests that they might be useful for PDT requiring lower photosensitizer concentration and reduced energy deposited through less light exposure.Article Gas-Phase Fragmentation Reactions of A7 Ions Containing a Glutamine Residue(Wiley-Blackwell, 2021) Atik, Ahmet; Arslanoğlu, Alper; Arslanoğlu, Alper; Yalçın, Talat; Yalçın, Talat; Atik, Ahmet; Arslanoğlu, Alper; Yalçın, Talat; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyThe gas-phase fragmentation reactions of the a7 ions derived from glutamine (Q) containing model heptapeptides have been studied in detail with low-energy collision-induced dissociation (CID) tandem mass spectrometry (MS/MS). Specifically, the positional effect of the Q residue has been investigated on the fragmentation reactions of a7 ions. The study involves two sets of permuted isomers of the Q containing model heptapeptides. The first set contains the QAAAAAA sequence, and the second set involves of QYAGFLV sequence, where the position of the Q residue is changed from N- to C-terminal gradually for both peptide series. An intense loss of ammonia from the a7 ions followed by internal amino acid eliminations strongly supports forming the imine-amides structure via cyclization/rearrangement reaction for all studied a7 ions. This is in agreement with the pioneering study reported by Bythell et al. (2010, 10.1021/ja101556g). A novel rearrangement reaction is detected upon fragmentation of imine-amide structure, which yields a protonated C-terminal amidated hexapeptide excluding the Q residue. A possible fragmentation mechanism was proposed to form the protonated C-terminal amidated hexapeptide, assisted via nucleophilic attack of the side chain amide nitrogen of the Q residue on its N-protonated imine carbon atom of the rearranged imine-amide structure. Highlights: The gas-phase fragmentation reactions of a7 ions obtained from protonated model peptides containing glutamine residue were studied by ESI-MS/MS. A rearranged imine-amide structure is the predominant even for a7 ions. Novel rearrangement reaction is observed which forms a protonated C-terminal amidated hexapeptide excluding Q residue upon fragmentation of the imine-amide structure.Article Citation - WoS: 2Citation - Scopus: 2Novel 2 '-alkoxymethyl Substituted Klavuzon Derivatives as Inhibitors of Topo I and Crm1(Academic Press, 2020) Çetinkaya, Hakkı; Çağır, Ali; Yıldız, Mehmet Salih; Kutluer, Meltem; Alkan, Aylin; Otaş, Hasan Ozan; Çağır, Ali; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyIn this work, 2'-alkoxymethyl substituted klavuzon derivatives were prepared starting from 2-methyl-1-naphthoic acid in eight steps. Anticancer potencies of the synthesized compounds were evaluated by performing MTT cell viability test over cancerous and healthy pancreatic cell lines, along with CRM1 inhibitory properties in HeLa cells by immunostaining and Topo I inhibition properties by supercoiled DNA relaxation assay. Their cytotoxic activities were also presented in hepatocellular carcinoma cells (HuH-7) derived 3D spheroids. Among the tested klavuzon derivatives, isobutoxymethyl substituted klavuzon showed the highest selectivity of cytotoxic activity against pancreatic cancer cell line. They showed potent Topo I inhibition while their CRM1 inhibitory properties somehow diminished compared to 4'-alkylsubstituted klavuzons. The most cytotoxic 2'-methoxymethyl derivative inhibited the growth of the spheroids derived from HuH-7 cell lines and PI staining exhibited time and concentration dependent cell death in 3D spheroids.Article Citation - WoS: 10Citation - Scopus: 11A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices(Elsevier, 2020) Gökçe, Begüm; Çağır, Ali; Akçok, İsmail; Pesen Okvur, Devrim; Çağır, Ali; Pesen Okvur, Devrim; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyDrug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.Article Citation - WoS: 2Citation - Scopus: 2Changes in Protein Profiles of Multiple Myeloma Cells in Response To Bortezomib(Informa Healthcare, 2013) Turan, Taylan; Şanlı Mohamed, Gülşah; Şanlı Mohamed, Gülşah; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyThe objective of this study was to determine the changes in protein profiles of U-266 multiple myeloma cells in response to bortezomib. Bortezomib inhibited cell proliferation and increased the loss of mitochondrial membrane potential and caspase-3 activity in a dose-dependent manner. DECODON Delta2D Version 4.3 software demonstrated 37 differentially expressed protein spots: five proteins were newly formed, 10 proteins were lost, 12 proteins were up-regulated and 10 proteins were down-regulated in bortezomib-treated cells as compared to untreated cells. Some of the identified proteins after mass spectrometric analysis were as follows: apoptosis regulatory protein Siva (newly formed), caspase recruitment domain-containing protein 14 (lost), Ras-related protein Rab-25 (up-regulated), nuclear factor κB (NF-κB) p105 subunit (down-regulated). In summary, differentially expressed proteins of MM U-266 cells in response to bortezomib were analyzed and identified. The data obtained from this study may indicate the use of bortezomib for the treatment of various diseases.Article Citation - WoS: 4Citation - Scopus: 7The Importance of Protein Profiling in the Diagnosis and Treatment of Hematologic Malignancies(Galenos Yayıncılık, 2011) Şanlı Mohamed, Gülşah; Turan, Taylan; Şanlı Mohamed, Gülşah; Baran, Yusuf; Ekiz, Hüseyin Atakan; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyProteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemiaassociated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high-throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed.Article Citation - WoS: 11Citation - Scopus: 14Proteomic Changes During Boron Tolerance in Barley (hordeum Vulgare) and the Role of Vacuolar Proton-Translocating Atpase Subunit E(Türkiye Klinikleri Journal of Medical Sciences, 2011) Atik, Ahmet Emin; Bozdağ, Gönensin Ozan; Koç, Ahmet; Kaya, Alaattin; Koç, Ahmet; Yalçın, Talat; Karakaya, Hüseyin Çağlar; Karakaya, Hüseyin Çağlar; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyBoron is an essential micronutrient for plants and animals; however, it can be toxic when present at high concentrations. The purpose of this study was to understand the mechanisms of boron tolerance in the Turkish barley (Hordeum vulgare) Anadolu cultivar. For this purpose, 2-dimensional electrophoresis (2-DE) was used to screen differentially expressed proteins for both control and boron-stressed Anadolu barley genotypes. Seven proteins were revealed by 2-DE: 1) ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCo large chain), 2) TLP5, a thaumatin-like protein, 3) PR5, a basic pathogenesis-related protein, 4) a RNase S-like protein, 5) a PSI type III chlorophyll a/b-binding protein, 6) a light-harvesting complex I LHC I, and 7) the vacuolar proton-translocating ATPase subunit E protein. These were found to be upregulated in response to boron treatment. Even though the protein encoded by the V-ATPase subunit E gene was overexpressed, its transcript level was downregulated by boron treatment. Heterologous expression of the barley V-ATPase subunit E gene in yeast provided boron resistance to yeast cells. These results indicated that the V-ATPase subunit E gene was functional and conferred tolerance to toxic boron levels in yeast and might play a role in the overall boron tolerance of barley. © TÜBITAK.Article Citation - WoS: 20Citation - Scopus: 20Genome-Wide Identification of Genes That Play a Role in Boron Stress Response in Yeast(Elsevier Ltd., 2011) Uluışık, İrem; Kaya, Alaattin; Karakaya, Hüseyin Çağlar; Avşar, Kadir; Karakaya, Hüseyin Çağlar; Koç, Ahmet; Koç, Ahmet; Yalçın, Talat; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyBoron is an essential micronutrient for plants and it is either necessary or beneficial for animals. Studies identified only few genes related to boron metabolism thus far and details of how boron is imported into cells and used in cell metabolism are largely unknown. In order to identify genes that play roles in boron metabolism, we screened the entire set of yeast haploid deletion mutants and identified 6 mutants that were resistant to toxic levels of boron, and 21 mutants that were highly sensitive to boron treatment. Furthermore, we performed a proteomic approach to identify additional proteins that are significantly up-regulated by boron treatment. Our results revealed many genes and pathways related to boron stress response and suggest a possible link between boron toxicity and translational control.Article Citation - WoS: 23Citation - Scopus: 26Development of Practical Hplc Methods for the Separation and Determination of Eggplant Steroidal Glycoalkaloids and Their Aglycones(Taylor and Francis Ltd., 2008) Eanes, Ritchie C.; Tek, Neslihan; Doğanlar, Sami; Frary, Anne; Doğanlar, Sami; Eanes, Ritchie C.; Frary, Anne; Tek, Neslihan; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyA practical set of HPLC methods was developed for the separation and determination of the eggplant steroidal glycoalkaloids, solanine, chaconine, solasonine, solamargine, and their aglycones, solasodine and solanidine. A gradient method was initially developed, but proved to be neither robust nor practical. Three separate isocratic methods using acetonitrile and ammonium dihydrogen phosphate were developed and shown to be more repeatable, less subject to fluctuations in mobile phase composition, and less time consuming. The effect of adjusting buffer pH, column temperature, and buffer type (triethylammonium phosphate vs. ammonium dihydrogen phosphate) were evaluated. It was also discovered that, by addition of 10% methanol to the acetonitrile portion of the mobile phase, more control over the separations was possible. The use of methanol as a mobile phase entrainer greatly improved separations in some cases and its effectiveness was also dependent upon column temperature. Assessments of the method recovery, limit of detection, and limit of quantitation were made using extracts from S. melongena and S. linnaeanum.