A Pro-Fluorescent Ubiquitin-Based Probe to Monitor Cysteine-Based E3 Ligase Activity

Protein post-translational modification with ubiquitin (Ub) is a versatile signal regulating almost all aspects of cell biology, and an increasing range of diseases is associated with impaired Ub modification. In this light, the Ub system offers an attractive, yet underexplored route to the development of novel targeted treatments. A promising strategy for small molecule intervention is posed by the final components of the enzymatic ubiquitination cascade, E3 ligases, as they determine the specificity of the protein ubiquitination pathway. Here, we present UbSRhodol, an autoimmolative Ub-based probe, which upon E3 processing liberates the pro-fluorescent dye, amenable to profile the E3 transthiolation activity for recombinant and in cell-extract E3 ligases. UbSRhodol enabled detection of changes in transthiolation efficacy evoked by enzyme key point mutations or conformational changes, and offers an excellent assay reagent amenable to a high-throughput screening setup allowing the identification of small molecules modulating E3 activity.     

A Magnetic Bio-Inspired Soft Carrier as a Temperature-Controlled Gastrointestinal Drug Delivery System

Currently, gastrointestinal bleeding in the colon wall and the small bowel is diagnosed and treated with endoscopes. However, the locations of this condition are often problematic to treat using traditional flexible and tethered tools. New studies commonly consider untethered devices for solving this problem. However, there still exists a gap in the extant literature, and more research is needed to diagnose and deliver drugs in the lower gastrointestinal tract using soft robotic carriers. This paper discusses the development of an untethered, magnetically-responsive bio-inspired soft carrier. A molding process is utilized to produce prototypes from Diisopropylidene-1,6-diphenyl-1,6-hexanediol-based Polymer with Ethylene Glycol Dimethacrylate (DiAPLEX) MP-3510 - a shape memory polymer with a low transition temperature to enable the fabrication of these carriers. The soft carrier design is validated through simulation results of deformation caused by magnetic elements embedded in the carrier in response to an external field. The thermal responsiveness of the fabricated prototype carriers is assessed ex vivo and in a phantom. The results indicate a feasible design capable of administering drugs to a target inside a phantom of a large intestine. The soft carrier introduces a method for the controlled release of drugs by utilizing the rubbery modulus of the polymer and increasing the recovery force through magnetic actuation.     

Tetracyanobutadiene Bridged Push-Pull Chromophores: Development of New Generation Optoelectronic Materials

This review describes the design strategies used for the synthesis of various tetracyanobutadiene bridged donor-acceptor molecular architectures by a click type [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction sequence. The photophysical and electrochemical properties of the tetracyanobutadiene bridged molecular architectures based on various moieties including diketopyrrolopyrrole, isoindigo, benzothiadiazole, pyrene, pyrazabole, truxene, boron dipyrromethene (BODIPY), phenothiazine, triphenylamine, thiazole and bisthiazole are summarized. Further, we discuss some important applications of the tetracyanobutadiene bridged derivatives in dye sensitized solar cells, bulk heterojunction solar cells and photothermal cancer therapy.