Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed β,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.
Photochemistry is a fast growing research field and many transformations previously not accessible to chemists now have become part of an ever growing standard repertoire. The limiting factors for a photoreactor system however are the possibility to perform stirring, removal of excess heat and the irradiation with UV or visible light -all that within a secure surrounding. Systems for starters may be as expensive as several thousand Euro. Here we design and assemble a LED photoreactor using scrap and standard materials, spending less than 30 E for a LED. The system may be adjusted to any required wavelength and its assembly is shown for the use of a 400 nm LED. To demonstrate its application, we then exemplarily use the reactor in the removal of a photolabile protection group during the synthesis of a SARS-CoV-2 spike protein glycopeptide.
Thermal recovery methods, in particular technology based on steam injection, are used extensively around the world for heavy oil and bitumen production. Because of the unconsolidated nature of the majority of such deposits, sand control is required. Design effectiveness of sand control depends on the reservoir type, production technology and operational practices. The industry is facing many challenges such as low oil prices, tight environmental regulations, the need to lower risks while assuring well integrity and longevity and project economics. All of that requires special technical solutions for thermal well design, including sand control. The paper provides an overview of sand control for thermal heavy oil and bitumen production operations, factors affecting sand control design for thermal projects, sand control devices and industry trends. Laboratory observations and field data are discussed. The impact of steam on different quality heavy oil and bitumen deposits in relation to sand control is discussed in detail. Efficient sand control design for thermal production operations requires a multidisciplinary approach and is an integral part of the well longevity and project economics. Better understanding of the impact of reservoir quality, thermal formation damage and operational practices on well performance is required to assure success of a thermal project.
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