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New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel?Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent. 相似文献
3.
Ekici OD Karla A Paetzel M Lively MO Pei D Dalbey RE 《The Journal of biological chemistry》2007,282(1):417-425
Signal peptidase functions to cleave signal peptides from preproteins at the cell membrane. It has a substrate specificity for small uncharged residues at -1 (P1) and aliphatic residues at the -3 (P3) position. Previously, we have reported that certain alterations of the Ile-144 and Ile-86 residues in Escherichia coli signal peptidase I (SPase) can change the specificity such that signal peptidase is able to cleave pro-OmpA nuclease A in vitro after phenylalanine or asparagine residues at the -1 position (Karla, A., Lively, M. O., Paetzel, M. and Dalbey, R. (2005) J. Biol. Chem. 280, 6731-6741). In this study, screening of a fluorescence resonance energy transfer-based peptide library revealed that the I144A, I144C, and I144C/I86T SPase mutants have a more relaxed substrate specificity at the -3 position, in comparison to the wild-type SPase. The double mutant tolerated arginine, glutamine, and tyrosine residues at the -3 position of the substrate. The altered specificity of the I144C/I86T mutant was confirmed by in vivo processing of pre-beta-lactamase containing non-canonical arginine and glutamine residues at the -3 position. This work establishes Ile-144 and Ile-86 as key P3 substrate specificity determinants for signal peptidase I and demonstrates the power of the fluorescence resonance energy transfer-based peptide library approach in defining the substrate specificity of proteases. 相似文献
4.
Studies on the macroscopic protonation constants of some alpha-amino acids in ethanol-water mixtures
Both to demonstrate whether the predominant species are dipolar ion or the neutral form and to predict the change of dipolar form to neutral form ratio in ethanol-water mixtures, the macroscopic protonation constants of eight alpha-amino acid (glycine, L-alanine, L-valine, L-leucine, L-phenylalanine, L-serine, L-methionine, and L-isoleucine) were determined potentiometrically in 20-80% (v/v) ethanol-water mixtures at 25 degrees C with an ionic strength of 0.10 M. The calculation of the constants was carried out using a PKAS computer program. The effect of solvent composition on the protonation constants and the dipolar ionic to neutral form ratio of these acids in the mixed solvents are discussed. One can conclude that the dipolar form of amino acids, HA(+/-), dominates in ethanol-water mixtures. 相似文献
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Irem Dogan Turacli Haldun Umudum Arzu Pampal Tuba Candar Lara Kavasoglu Yaren Sari 《Molecular biology reports》2018,45(3):195-201
There is a growing body of evidence about metformin being effective in cancer therapy. Despite controversies about the ways of its effectiveness, several ongoing clinical trials are evaluating the drug when used as an adjuvant or a neo-adjuvant agent. We aimed to investigate metformin’s effects on proliferation, metastasis, and hormone receptor expressions in breast cancer cell line MCF-7 incubated in two different glucose conditions. MCF-7 cells were incubated in high or low glucose media and treated with various doses of metformin. The cell viability was studied using MTT test. The Ki-67, estrogen and progesterone receptor expression were evaluated by ICC and galectin-3 expression was evaluated by ELISA or spectrophotometrically. The cell viability following consecutive metformin doses in either glucose condition for 24 and 48 h represented a significant decrease when compared to control. The proliferation detected in low glucose medium following metformin at doses < 20 mM was found significantly decreased when compared to high glucose medium at 48 h. In terms of galectin-3 levels, the increase in high glucose medium treated with metformin and the decrease in low glucose medium were found statistically significant when compared to control. Progesterone receptor staining demonstrated a significant increase in low glucose medium. Our findings represent better outcomes for cancer lines incubated in low glucose medium treated with metformin in terms of viability, receptor expression and metastatic activity, and highlight the potential benefit of metformin especially in restraining the cancer cell’s ability to cope energetic stress in low glucose conditions. 相似文献
7.
Yavuz N Unal E Dogan M Kiziler AR Aydemir B Titiz I 《Biological trace element research》2005,106(3):205-209
Serum free prostate-specific antigen (fPSA) is the most useful tumor marker for prostatic cancer screening. However, recently,
fPSA has also been detected in sera from patients with pancreatic diseases. In addition, it has been shown that zinc (Zn)
concentration might change in both serum and tissues in pancreatic disease. In the present study, we measured serum concentrations
of fPSA and Zn as possible markers and prognostic factors in an experimental acute-pancreatitis model. Twenty-five female
Wistar albino rats were divided into two groups: the control group (n=10) and the experimental group (n=15). Acute pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. The animals were sacrificed
24 h later to detect the concentrations of serum fPSA and Zn. fPSA values were detected to be significantly higher in the
experimental group p<0.001). There was also a significant decrease in the serum Zn level of the acute-pancreatitis group (p<0.001). In conclusion, these findings suggested that a combination of these parameters might represent a significant improvement
on the diagnostic value of each of them separately and provide a powerful tool for differential diagnosis and prognosis in
pancreatic diseases. 相似文献
8.
Nucci NV Marques BS Bédard S Dogan J Gledhill JM Moorman VR Peterson RW Valentine KG Wand AL Wand AJ 《Journal of biomolecular NMR》2011,50(4):421-430
Comprehensive application of solution NMR spectroscopy to studies of macromolecules remains fundamentally limited by the molecular
rotational correlation time. For proteins, molecules larger than 30 kDa require complex experimental methods, such as TROSY
in conjunction with isotopic labeling schemes that are often expensive and generally reduce the potential information available.
We have developed the reverse micelle encapsulation strategy as an alternative approach. Encapsulation of proteins within
the protective nano-scale water pool of a reverse micelle dissolved in ultra-low viscosity nonpolar solvents overcomes the
slow tumbling problem presented by large proteins. Here, we characterize the contributions from the various components of
the protein-containing reverse micelle system to the rotational correlation time of the encapsulated protein. Importantly,
we demonstrate that the protein encapsulated in the reverse micelle maintains a hydration shell comparable in size to that
seen in bulk solution. Using moderate pressures, encapsulation in ultra-low viscosity propane or ethane can be used to magnify
this advantage. We show that encapsulation in liquid ethane can be used to reduce the tumbling time of the 43 kDa maltose
binding protein from ~23 to ~10 ns. These conditions enable, for example, acquisition of TOCSY-type data resolved on the adjacent
amide NH for the 43 kDa encapsulated maltose binding protein dissolved in liquid ethane, which is typically impossible for
proteins of such size without use of extensive deuteration or the TROSY effect. 相似文献
9.
Naima?Zemirli Marie?Pourcelot Neslihan?Dogan Aimé?Vazquez Damien?ArnoultEmail author 《Cell communication and signaling : CCS》2014,12(1):72
Background
The nuclear factor κB (NF-κB) family members regulate several biological processes as cell proliferation and differentiation, inflammation, immunity and tumor progression. Ubiquitination plays a key role in NF-κB activation and the ubiquitylated transmitters of the NF-κB signaling cascade accumulate in close proximity to endomembranes.Findings
We performed an unbiased siRNA library screen targeting the 46 E3 ubiquitin ligases bearing transmembrane domains to uncover new modulators of NF-κB activation, using tumor necrosis factor–α (TNF-α) receptor (TNFR) stimulation as a model. We report here the identification of a new Golgi Apparatus-resident protein, RNF121, as an enhancer of NF-κB promoter activity through the catalytic function of its RING domain. From a molecular standpoint, while knocking down RNF121 did not alter RIP1 ubiquitination and IKK activation, the proteasomal degradation of IκBα was impaired suggesting that this E3 ubiquitin ligase regulates this process. However, RNF121 did not directly ubiquitinate IκBα While they were found in the same complex. Finally, we discovered that RNF121 acts as a broad regulator of NF-κB signaling since its silencing also dampens NF-κB activation following stimulation of Toll-Like Receptors (TLRs), Nod-Like Receptors (NLRs), RIG-I-Like Receptors (RLRs) or after DNA damages.Conclusions
These results unveil an unexpected role of Golgi Apparatus and reveal RNF121 as a new player involved in the signaling leading to NF-κB activation.10.
Dr. Ayse Demirbas Dr. Baris Karsli Seyma Dadi Dr. Nihan Arabacı Dr. Fatih Dogan Koca Prof. Dr. M. Gokhan Halici Prof. Dr. Ismail Ocsoy 《化学与生物多样性》2023,20(8):e202300090
This work describes a unique and environmentally friendly approach for creating three-dimensional (3D) organic-inorganic flower shaped hybrid nanostructures called “nanoflower (NF)” by using Umbilicaria decussate (U. decussate) extract and copper ions (Cu2+). U. decussate species were collected from certain place in Antarctic and Turkey and extraction of each species were completed in methanol and water. The U. decussate extracts were used as organic components and Cu2+ acted as inorganic components for formation of U. decussate extracts based hybrid NFs. We rationally used these NFs as novel nanobiocatalyst and antimicrobial agents. These NFs exhibited peroxidase mimic, dye degradation and antimicrobial properties. The NFs were characterized with various techniques. For instance, the morphologies of the NFs were monitored by scanning electron microscope (SEM), presence of elements in the NFs were presented using Energy Dispersive X-Ray Analysis (EDX). Fourier-transform infrared spectroscopy (FT-IR) was used to elucidate corresponding bending and stretching of bonds in the NFs. The NFs acted as effective Fenton agents in the presence of hydrogen peroxide, and we demonstrated their peroxidase-like activity against guaiacol, dye degradation property towards malachite green and antimicrobial activity for Aeromonas hydrophila, Aeromonas sobria, Escherichia coli, Salmonella enterica and Staphylococcus aureus. 相似文献