Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis,Complexing Abilities and Antiproliferative Properties

Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent.     

Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids

The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)_n-O2Oc-NH₂, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]₈-O2Oc-NH₂ and typical for large proteins.     

iPSC-Cardiomyocyte Models of Brugada Syndrome—Achievements,Challenges and Future Perspectives

Brugada syndrome (BrS) is an inherited cardiac arrhythmia that predisposes to ventricular fibrillation and sudden cardiac death. It originates from oligogenic alterations that affect cardiac ion channels or their accessory proteins. The main hurdle for the study of the functional effects of those variants is the need for a specific model that mimics the complex environment of human cardiomyocytes. Traditionally, animal models or transient heterologous expression systems are applied for electrophysiological investigations, each of these models having their limitations. The ability to create induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), providing a source of human patient-specific cells, offers new opportunities in the field of cardiac disease modelling. Contemporary iPSC-CMs constitute the best possible in vitro model to study complex cardiac arrhythmia syndromes such as BrS. To date, thirteen reports on iPSC-CM models for BrS have been published and with this review we provide an overview of the current findings, with a focus on the electrophysiological parameters. We also discuss the methods that are used for cell derivation and data acquisition. In the end, we critically evaluate the knowledge gained by the use of these iPSC-CM models and discuss challenges and future perspectives for iPSC-CMs in the study of BrS and other arrhythmias.     

Adsorptive removal of technetium‐99 using macroporous poly(GMA‐co‐EGDMA) modified with diethylene triamine

The possibility of sorption of technetium‐99 in the form of pertechnetate anion (TcO₄^?) and the sorption kinetics for removing TcO₄^? from aqueous solution by chelating polymers based on glycidyl methacrylate (GMA) were investigated. Two samples of macroporous crosslinked poly(glycidyl methacrylate‐co‐ethylene glycol dimethacrylate) (PGME), with different amount of the crosslinker (ethylene glycol dimethacrylate, EGDMA), were synthesized by suspension copolymerization and functionalized with diethylene triamine (deta). We propose that nonspecific sorption of pertechnetate anion via electrostatic interactions takes place at the protonated amino groups of macroporous crosslinked copolymer. The results of batch experiments performed at pH 1–14 showed fast sorption kinetics for removing TcO₄^? by amino‐functionalized PGME‐deta in a wide range of pH, that is, from 1.0 to 9.0. Almost complete removal of TcO₄^? (91–98%) was reached within 180 min in the stated pH range (1.0–9.0), with the sorption half‐times of under 25 min. The partitioning coefficients of linear adsorption isotherms, with 180‐min equilibrium time, reach the high values of 2130 mL g^?1 and 1698 mL g^?1 for the two samples of synthesized PGME‐deta. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Biodegradable poly(L‐lactic acid)/TiO2 nanocomposites: Thermal properties and degradation

Poly(L ‐lactic acid)‐titanium dioxide nanocomposites (with various loadings of TiO₂: 0.5, 1, 2, 5, and 10 wt %) were produced by solution casting method. The influence of TiO₂ on thermal properties and crystallinity of PLA was investigated by DSC and FTIR spectroscopy. The TiO₂ nano filler has no significant influence on the characteristic temperatures (T_g, T_c, and T_m), but has high impact on the crystallinity of these systems. The degree of crystallinity X_c significantly increases for PLA nanocomposites loaded with up to 5 wt % of TiO₂, while for 10 wt % load of TiO₂ it drops below X_c of the pure resin. The degradation of the prepared composites was evaluated hydrolytically in 1N NaOH, enzymatically in α‐amylase solutions, and under UV irradiation. The catalytic effect of TiO₂ nano particles on the degradation processes under UV light exposure (λ = 365 nm) and hydrolytic degradation was confirmed with the increase of the filler content. The opposite effect was identified in enzymatic degradation experiments. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Mispredicting and misremembering: Patients with renal failure overestimate improvements in quality of life after a kidney transplant.

Objective: People tend to overestimate the impact that future events will have on their quality of life. In the case of a medical treatment like kidney transplant, this should result in biased predictions--overestimates of how much the transplant will benefit quality of life. The authors surveyed kidney transplant patients, both before and after transplant, to test whether they would overestimate the benefits of a successful transplant for their quality of life. Design: The authors interviewed 307 patients on a waiting list for cadaveric renal or renal-pancreatic transplant, and 195 patients one year after a successful transplant. A sub sample of patients were interviewed both before and after transplant. Main Outcome Measures: The survey included measures of quality of life, both in terms of an overall estimate (0-100), and across sub domains, including health, employment, and travel. Results: Cross-sectional results suggested that overall quality of life improved after transplant, but the predictions of pretransplant patients overestimated the magnitude of the improvement (p     

Embedding asymmetric backdoors into the RSA key generator

Journal of Computer Virology and Hacking Techniques - This article describes the class of asymmetric backdoors in the RSA key generator. The algorithms are based on the classical Anderson’s...