The validation of new CHD1L inhibitors as a therapeutic strategy for cancer.

Chromodomain helicase DNA-binding protein 1 like (CHD1L) is an oncogene that promotes tumor progression, metastasis, and multidrug resistance. CHD1L expression is indicative of poor outcomes and low survival in cancer patients with various cancer types. Herein, we report a set of CHD1L inhibitors (CHD1Li) discovered from high-throughput screening and evaluated using enzyme inhibition, 3D tumor organoid cytotoxicity and mechanistic assays. The structurally distinct compounds 8-11 emerged as hits with promising bioactivity by targeting CHD1L. CHD1Li were further examined for their stability in human and mouse liver microsomes, which showed compounds 9 and 11 to be the most metabolically stable. Additionally, molecular modeling studies of CHD1Li with the target protein shed light on key pharmacophore features driving CHD1L binding. Taken together, these results expand the chemical space of CHD1Li as a potential targeted therapy for colorectal cancer and other cancers.

Development of gold plasmonic nanoparticles for detection of polydiallyldimethylammonium chloride at Umgeni water treatment plants: An optimised study and case application.

Background: Polydiallyldimethylammonium chloride (poly-(DADMAC) is used in many drinking water treatment plants in most parts of the world as a flocculant to remove suspended solids from raw water. However, it is very important that residual poly-(DADMAC) is monitored because it disintegrates into a carcinogenic compound known as N-nitrosodimethylamine (NDMA) during the treatment of drinking water. Methods: In this work, the gold nanoparticle method is optimised for the detection of poly-(DADMAC), where the gold nanoparticles were stabilised with trisodium citrate and then used in quantifying poly-(DADMAC) by Ultraviolet-Visible-Near Infrared spectrophotometry. The optimised method was able to measure poly-(DADMAC) at low concentrations of 1.000 µg L-1 in drinking water with limits of detection and limits of quantification of 0.3302 and 1.101 µg L-1, respectively. Significant results: The method was applied to two different water treatment plants and the concentration of poly-(DADMAC) found during stages of the water treatment process ranged from 1.013 to 33.63 µg L-1. The average poly-(DADMAC) concentrate concentration that is dosed for coagulation in Umgeni Water plant A was 7.889 µg L-1 while in plant B was 19.28 µg L-1. Residual poly-(DADMAC) concentration in drinking water was within the accepted limit of 50.00 µg L-1, regulated by the World Health Organisation (WHO).

A Practical Peptide Synthesis Workflow Using Amino-Li-Resin.

Herein we report a practical approach for peptide synthesis using second-generation fibrous polyacrylamide resin (Li-resin, "Li" is coming from the name of its inventor, Yongfu Li). This resin with the corresponding handle was used for solid phase peptide synthesis (SPPS) using a fluorenylmethoxycarbonyl (Fmoc) approach. We reveal that the most appropriate mixing and filtration strategy when using amino-Li-resin in SPPS is via shaking and gravity filtration, instead of mechanical stirring and suction filtration used with other resins. The strategy was demonstrated with the SPPS of H-Tyr-Ile-Ile-Phe-Leu-NH2, which contains the difficult sequence Ile-Ile. The peptide was obtained with excellent purity and yield. We are confident that this strategy will be rapidly implemented by other peptide laboratories.