Design,Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.     

A short guide to topological terms in the effective theories of condensed matter

This article is meant as a gentle introduction to the topological terms that often play a decisive role in effective theories describing topological quantum effects in condensed matter systems. We first take up several prominent examples, mainly from the area of quantum magnetism and superfluids/superconductors. We then briefly discuss how these ideas are now finding incarnations in the studies of symmetry-protected topological phases, which are in a sense a generalization of the concept of topological insulators to a wider range of materials, including magnets and cold atoms.     

Input-output linearization of retarded non-linear systems by using an extension of Lie derivative

This paper considers the input-output linearization problem for retarded non-linear systems, which have time-delays in the state. By using an extension of the Lie derivative for functional differential equations, we derive a coordinates transformation and a static state feedback to obtain linear input-output behaviour for a class of retarded non-linear systems. The obtained coordinates transformation is allowed to contain not only the current value of the state variables but also the past values of ones. In addition, we show that the coordinates transformation is invertible in a neighbourhood of the origin and examine the stability condition of the closed loop system with the static state feedback. The effectiveness of the proposed technique is demonstrated through numerical simulations.     

A bona fide two-dimensional percolation model: an insight into the optimum photoactivator concentration in La2/3-xEuxTa2O7 nanosheets

La–Eu solid solution nanosheets La_2/3−xEu_xTa₂O₇ have been synthesized, and their photoluminescence properties have been investigated. La_2/3−xEu_xTa₂O₇ nanosheets were prepared from layered perovskite compounds Li₂La_2/3−xEu_xTa₂O₇ as the precursors by soft chemical exfoliation reactions. Both the precursors and the exfoliated nanosheets exhibit a decrease in intralayer lattice parameters as the Eu contents increase. However, there is a discontinuity in this trend between the nominal Eu content ranges x≤ 0.3 and x ≥ 0.4. This discontinuity is attributed to the difference in degree of TaO₆ octahedra tilting for the La- and Eu-rich phases. La_2/3−xEu_xTa₂O₇ nanosheets exhibit red emission, characteristic of the f–f transitions in Eu³⁺ photoactivators. The photoluminescence emission can be obtained from both host and direct photoactivator excitation. However, photoluminescence emission through host excitation is much more dominant than that through direct photoactivator excitation, and this behavior is consistent with that of all the other rare-earth photoactivated nanosheets reported previously. The absolute photoluminescence quantum efficiency of the La_2/3−xEu_xTa₂O₇ nanosheets increases as the experimentally determined Eu contents increase up to x=0.45 and decrease above it. This result is in good agreement with the optimum photoactivator concentration expected from the percolation theory. These solid solution La_2/3−xEu_xTa₂O₇ nanosheets are excellent models for validating the theory of optimum photoactivator concentration in the truly two-dimensional photoactivator matrix.     

Liposome‐Based in Vitro Evolution of Aminoacyl‐tRNA Synthetase for Enhanced Pyrrolysine Derivative Incorporation

Methanosarcina species pyrrolysyl‐tRNA synthetase (PylRS) attaches Pyl to its cognate amber suppressor tRNA. The introduction of two mutations (Y384F and Y306A) into PylRS was previously shown to generate a mutant, designated LysZ‐RS, that was able to attach N‐benzyloxycarbonyl‐L ‐lysine (LysZ) to its cognate tRNA. Despite the potential of LysZ derivatives, further LysZ‐RS engineering has not been performed; consequently, we aimed to generate LysZ‐RS mutants with improved LysZ incorporation activity through in vitro directed evolution. Using a liposome‐based in vitro compartmentalization (IVC) approach, we screened a randomly mutagenized gene library of LysZ‐RS and obtained a mutant that showed increased LysZ incorporation activity both in vitro and in vivo. The ease and high flexibility of liposome‐based IVC should enable the evolution of not only LysZ‐RS that can attach various LysZ derivatives but also of other enzymes involved in protein translation.     

Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes

Post‐translational modification of histone tails plays critical roles in gene regulation. Thus, molecules recognizing histone tails and controlling their epigenetic modification are desirable as biochemical tools to elucidate regulatory mechanisms. There are, however, only a few synthetic ligands that bind to histone tails with substantial affinity. We report CA2 and CA3, which exhibited sub‐micromolar affinity to histone tails (especially tails with a trimethylated lysine). Multivalent display of trisulfonated calix[4]arene was important for strong binding. CA2 was applicable not only to synthetic tail peptides but also to endogenous histone proteins, and was successfully used to pull‐down endogenous histones from nuclear extract. These findings indicate the utility of these supramolecular ligands as biochemical tools for studying chromatin regulator protein and as a targeting motif in ligand‐directed catalysis to control epigenetic modifications.     

Lateral Inhomogeneity in the Electronic Structure of a Conjugated Poly(3‐hexylthiophene) Thin Film

How annealing influences the morphology of a highly regioregular poly(3‐hexylthiophene) (RR‐P3HT) film at the substrate interface as well as the lateral inhomogeneity in the electronic structure of the film are elucidated. Whereas previous studies have reported that high‐molecular‐weight (MW) RR‐P3HT films tend to show low crystallinity even after annealing, it is found that high‐MW RR‐P3HT does show high crystallinity after annealing at high temperature for a long time. Photoemission electron microscopy (PEEM), X‐ray photoemission spectroscopy, and ultraviolet photoemission spectroscopy results clearly resolve a considerable lateral inhomogeneity in the morphology of RR‐P3HT film, which results in a variation of the electronic structure depending on the local crystallinity. The PEEM results show how annealing facilitates crystal growth in a high‐MW RR‐P3HT film.     

ADSORPTION BEHAVIOR OF COBALT( II) IONS ON LAYERED DIHYDROGEN TETRATITANATE HYDRATE FIBERS IN AQUEOUS SOLUTIONS IN THE RANGE FROM 298 to 523 K

The adsorption properties of cobalt(II) ions have been studied on layered dihydrogen tetratitanate hydrate fibers, H₂Ti₄O₉,?nH₂O, in the temperature range from 298 to 523?K. The distribution coefficients of the adsorption of cobalt (II) ions were increased with increasing temperatures up to 367?K, but were decreased in the temperature range between 367 and 523?K. The X-ray powder diffraction patterns of the fibers indicate that the fibers hold layer structure up to 367?K, but change to low crystalline anatase or its precursor above that temperature. It is notable that the material has the capability of cobalt (II) adsorption even at 523?K, although the maximum is present at 367?K.