Experimental and computational insights into the mechanism of the copper(i)-catalysed sulfonylative Suzuki-Miyaura reaction.

A mechanistic study into the copper(i)-catalysed sulfonylative Suzuki-Miyaura reaction, incorporating sulfur dioxide, is described. Utilising spectroscopic and computational techniques, an exploration into the individual components of the competing catalytic cycles is delineated, including identification of the resting state catalyst, transmetalation of arylboronic acid onto copper(i), the sulfur dioxide insertion process, and the oxidative addition of aryl halide to Cu. Studies also investigated prominent side-reactions which were uncovered, including a competing copper(ii)-catalysed mechanism.

The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway.

Most cases of cystic fibrosis (CF) are caused by class 2 mutations in the cystic fibrosis transmembrane regulator (CFTR). These proteins preserve some channel function but are retained in the endoplasmic reticulum (ER). Partial rescue of the most common CFTR class 2 mutant, F508del-CFTR, has been achieved through the development of pharmacological chaperones (Tezacaftor and Elexacaftor) that bind CFTR directly.

Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives.

Dipolar aprotic and ethereal solvents comprise just over 40% of all organic solvents utilized in synthetic organic, medicinal, and process chemistry. Unfortunately, many of the common "go-to" solvents are considered to be "less-preferable" for a number of environmental, health, and safety (EHS) reasons such as toxicity, mutagenicity, carcinogenicity, or for practical handling reasons such as flammability and volatility. Recent legislative changes have initiated the implementation of restrictions on the use of many of the commonly employed dipolar aprotic solvents such as dimethylformamide (DMF) and -methyl-2-pyrrolidinone (NMP), and for ethers such as 1,4-dioxane.

Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer.

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer.

The Diverse Functions of Mutant 53, Its Family Members and Isoforms in Cancer.

The p53 family of proteins has grown substantially over the last 40 years. It started with p53, then p63, p73, isoforms and mutants of these proteins. The function of p53 as a tumour suppressor has been thoroughly investigated, but the functions of all isoforms and mutants and the interplay between them are still poorly understood.

Publisher Correction: Genomic instability in mutant p53 cancer cells upon entotic engulfment.

The original version of this article incorrectly omitted an affiliation of Patricia A. J. Muller: 'Cancer Research UK Manchester Institute, The University of Manchester | Alderley Park, Manchester, SK10 4TG, UK'.

Genomic instability in mutant p53 cancer cells upon entotic engulfment.

Cell-in-cell (CIC) structures are commonly seen in tumours. Their biological significance remains unclear, although they have been associated with more aggressive tumours. Here we report that mutant p53 promotes CIC via live cell engulfment.