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Publication Metadata only Chitosan in cancer therapy: a dual role as a therapeutic agent and drug delivery system(Walter de Gruyter Gmbh, 2024) Atmaca, Harika; Ilhan, Suleyman; N/A; Oğuz, Ferdi; Graduate School of Health SciencesAlthough chemotherapy is still the most preferred treatment for cancer, most chemotherapeutic agents target both cancer cells and healthy cells and cause serious side effects due to high toxicity. Improved drug delivery systems (DDSs), which enhance the efficacy of current chemotherapeutic drugs while reducing their toxicity, offer potential solutions to these challenges. Chitosan (CS) and its derivatives are biopolymers with biodegradable, biocompatible, and low-toxicity properties, and their structure allows for convenient chemical and mechanical modifications. In its role as a therapeutic agent, CS can impede the proliferation of tumor cells through the inhibition of angiogenesis and metastasis, as well as by triggering apoptosis. CS and its derivatives are also frequently preferred as DDSs due to their properties such as high drug-carrying capacity, polycationic structure, long-term circulation, and direct targeting of cancer cells. Various therapeutic agents linked to CS and its derivatives demonstrate potent anticancer effects with advantages such as reduced side effects compared to the original drugs, owing to factors like targeted distribution within cancer tissues and sustained release. This review emphasizes the utilization of CS and its derivatives, both as therapeutic agents and as carriers for established chemotherapeutic drugs.Publication Metadata only Evaluation of the biocompatibility of the GSH‑coated Ag2S quantum dots in vitro: a perfect example for the non-toxic optical probes(Springer, 2020) N/A; N/A; Department of Chemistry; N/A; Aydemir, Duygu; Hashemkhani, Mahshid; Acar, Havva Funda Yağcı; Ulusu, Nuriye Nuray; PhD Student; PhD Student; Faculty Member; Faculty Member; Department of Chemistry; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; College of Sciences; School of Medicine; N/A; N/A; 178902; 6807Near-infrared quantum dots (NIR QDs) are promising candidate for the fluorescent probes due to their better penetration depth, long-lived luminescence with size-tunable photoluminescence wavelengths. Glutathione-coated silver sulfide quantum dots (GSH-Ag2S QDs) were synthesized using AgNO3 and Na2S in the aqueous media and they can give reaction with glutathione reductase (GR) and glutathione-s transferase (GST) enzymes as acting substrate analogue in vitro. Investigation of the toxicity of the nanomaterials are necessary to use them in the medical field and biomedical applications. Thus, in this study we investigated biocompatibility of the GSH-Ag2S QDs in vitro using 293 T and CFPAC-1 cell lines. Cell viability by MTT assay, light microscopy, fluorescence microscopy, oxidative stress enzyme activities and ICP-MS analysis were performed to evaluate the cytotoxicity and internalization of the GSH-Ag2S QDs. GSH-Ag2S QDs showed great biocompatibility with both cell lines and did not cause imbalance in the oxidative stress metabolism. The ultralow solubility product constant of Ag2S QDs (K-sp = 6.3 x 10(-50)) prevents release of Ag ions into the biological systems that is in agreement with data obtained by ICP-MS. In conclusion, this data prove potential of GSH-Ag2S QDs as a biocompatible optical probe to be used for the detection and/or targeting of GSH impaired diseases including cancer. [GRAPHICS] .Publication Open Access Gaussian network model revisited: effects of mutation and ligand binding on protein behavior(Institute of Physics (IOP) Publishing, 2022) Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997The coarse-grained Gaussian network model (GNM), considers only the alpha carbons of the folded protein. Therefore it is not directly applicable to the study of mutation or ligand binding problems where atomic detail is required. This shortcoming is improved by including all atom pairs within the coordination shell of each other into the Kirchoff adjacency matrix. Counting all contacts rather than only alpha carbon contacts diminishes the magnitude of fluctuations in the system. But more importantly, it changes the graph-like connectivity structure, i.e., the Kirchoff adjacency matrix of the protein. This change depends on amino acid type which introduces amino acid specific and position specific information into the classical coarse-grained GNM which was originally modeled in analogy with the phantom network model of rubber elasticity. With this modification, it is now possible to explain the consequences of mutation and ligand binding on residue fluctuations, their pair-correlations and mutual information shared by each pair. We refer to the new model as 'all-atom GNM'. Using examples from published data we show that the all-atom GNM gives B-factors that are in better agreement with experiment, can explain effects of mutation on long range communication in PDZ domains and can predict effects of GDP and GTP binding on the dimerization of KRAS.Publication Metadata only In vitro interaction of glutathione S‐transferase‐pi enzyme with glutathione‐coated silver sulfide quantum dots: a novel method for biodetection of glutathione S‐transferase enzyme(Wiley, 2019) N/A; N/A; Department of Chemistry; N/A; Aydemir, Duygu; Hashemkhani, Mahshid; Acar, Havva Funda Yağcı; Ulusu, Nuriye Nuray; PhD Student; PhD Student; Faculty Member; Faculty Member; Department of Chemistry; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; College of Sciences; School of Medicine; N/A; N/A; 178902; 6807Quantum dots (QD) are being evaluated as inorganic nanoparticles for both in vitro and in vivo optical imaging. They are also used as sensors or vehicles for targeted drug delivery combined with optical imaging. In this study, we demonstrated that glutathione-coated Ag2S QDs (GSH-Ag2S QDs) act as a substrate analogue of glutathione S-transferase (GST) enzymes for the first time in the literature. The GSTs belong to a major group of detoxification enzymes involved in the detoxification metabolism responsible for the protection of cells against reactive oxygen species (ROS) or electrophiles. GST isozymes are impaired in the various diseases such as neurological diseases and cancer. We evaluated the interaction of GST-pi enzyme with GSH-Ag2S QDs, which have never been studied in the literature before, using both fluorometric and spectrophotometric methods. Our data showed that GSH-Ag2S QDs gave reaction with GST enzyme as a substrate analogue. In conclusion, our data may help to guide researchers for further development of sensing systems for GST activity which is impaired in various diseases including cancer.Publication Open Access Interaction prediction and classification of PDZ domains(BioMed Central, 2010) Kalyoncu, Sibel; Keskin, Özlem; Gürsoy, Attila; Master Student; Faculty Member; The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; N/A; 26605; 8745Background: PDZ domain is a well-conserved, structural protein domain found in hundreds of signaling proteins that are otherwise unrelated. PDZ domains can bind to the C-terminal peptides of different proteins and act as glue, clustering different protein complexes together, targeting specific proteins and routing these proteins in signaling pathways. These domains are classified into classes I, II and III, depending on their binding partners and the nature of bonds formed. Binding specificities of PDZ domains are very crucial in order to understand the complexity of signaling pathways. It is still an open question how these domains recognize and bind their partners. Results: The focus of the current study is two folds: 1) predicting to which peptides a PDZ domain will bind and 2) classification of PDZ domains, as Class I, II or I-II, given the primary sequences of the PDZ domains. Trigram and bigram amino acid frequencies are used as features in machine learning methods. Using 85 PDZ domains and 181 peptides, our model reaches high prediction accuracy (91.4%) for binary interaction prediction which outperforms previously investigated similar methods. Also, we can predict classes of PDZ domains with an accuracy of 90.7%. We propose three critical amino acid sequence motifs that could have important roles on specificity pattern of PDZ domains. Conclusions: Our model on PDZ interaction dataset shows that our approach produces encouraging results. The method can be further used as a virtual screening technique to reduce the search space for putative candidate target proteins and drug-like molecules of PDZ domains.Publication Open Access Mode coupling points to functionally important residues in myosin II(Wiley, 2014) Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Physics; Varol, Onur; Yüret, Deniz; Erman, Burak; Kabakçıoğlu, Alkan; Faculty Member; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Physics; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; 179996; 179997; 49854Relevance of mode coupling to energy/information transfer during protein function, particularly in the context of allosteric interactions is widely accepted. However, existing evidence in favor of this hypothesis comes essentially from model systems. We here report a novel formal analysis of the near-native dynamics of myosin II, which allows us to explore the impact of the interaction between possibly non-Gaussian vibrational modes on fluctutational dynamics. We show that an information-theoretic measure based on mode coupling alone yields a ranking of residues with a statistically significant bias favoring the functionally critical locations identified by experiments on myosin II.Publication Metadata only Retinoic acid reduces kidney injury by regulating oxidative stress, NRF-2, and apoptosis in hyperoxic mice(Wiley, 2024) Bayrak, Bertan Boran; Yıldırım, Merve; Yanardağ, Refiye; Öztay, Füsun; Kayalar, Özgecan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)Nuclear factor-erythroid-2-related factor-2 (NRF-2) is a cellular resistance protein to oxidants. We investigated the effect of exogenous all-trans retinoic acid (ATRA) on the antioxidant system and NRF-2 in mice kidneys under hyperoxia-induced oxidative stress. Mice were divided into four groups. Daily, two groups were given either peanut-oil/dimethyl sulfoxide (PoDMSO) mixture or 50 mg/kg ATRA. Oxidative stress was induced by hyperoxia in the remaining groups. They were treated with PoDMSO or ATRA as described above, following hyperoxia (100% oxygen) for 72 h. NRF-2 and active-caspase-3 levels, lipid peroxidation (LPO), activities of antioxidant enzymes, xanthine oxidase (XO), paraoxonase1 (PON1), lactate dehydrogenase (LDH), tissue factor (TF), and prolidase were assayed in kidneys. Hyperoxia causes kidney damage induced by oxidative stress and apoptosis. Increased LPO, LDH, TF, and XO activities and decreased PON1 and prolidase activities contributed to kidney damage in hyperoxic mice. After hyperoxia, increases in the activities of antioxidant enzymes and NRF-2 level could not prevent this damage. ATRA attenuated damage via its oxidative stress-lowering effect. The decreased LDH and TF activities increased PON1 and prolidase activities, and normalized antioxidant statuses are indicators of the positive effects of ATRA. We recommend that ATRA can be used as a renoprotective agent against oxidative stress induced-kidney damage. This study investigates the protective effects of all-trans retinoic acid (ATRA) against oxidative stress and oxidative stress-induced tissue damage in mouse kidneys. Exposure to high oxygen levels significantly damages kidney tissues by increasing lipid peroxidation and enzyme activities, leading to cellular dysfunction. However, treatment with ATRA demonstrated a remarkable ability to attenuate these effects, increase the activity of antioxidant defenses, and stabilize essential renal enzymes. These findings suggest that ATRA may be a potent renoprotector and offer a promising approach to managing oxidative stress-induced renal damage.