Recombinant mammalian host cell lines, in particular CHO and HEK293 cells, are used for the industrial production of therapeutic proteins. Despite their well-known genomic instability, the control mechanisms that enable cells to respond to changes in the environmental conditions are not yet fully understood, nor do we have a good understanding of the factors that lead to phenotypic shifts in long-term cultures. A contributing factor could be inherent diversity in transcriptomes within a population.
View Article and Find Full Text PDFAnastellin, a recombinant protein fragment from the first type III module of fibronectin, mimics a partially unfolded intermediate implicated in the assembly of fibronectin fibrils. Anastellin influences the structure of fibronectin and initiates in vitro fibrillation, yielding "superfibronectin", a polymer with enhanced cell-adhesive properties. This ability is absent in an anastellin double mutant, L37AY40A.
View Article and Find Full Text PDFα,β-Unsaturated carbonyls are a common motif in environmental toxins (e.g. acrolein) as well as therapeutic drugs, including dimethylfumarate (DMFU) and monomethylfumarate (MMFU), which are used to treat multiple sclerosis and psoriasis.
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September 2022
Humans have widespread exposure to both oxidants, and soft electrophilic compounds such as alpha,beta-unsaturated aldehydes and quinones. Electrophilic motifs are commonly found in a drugs, industrial chemicals, pollutants and are also generated via oxidant-mediated degradation of biomolecules including lipids (e.g.
View Article and Find Full Text PDFHumans are commonly exposed to α,β-unsaturated carbonyls as both environmental toxins (e.g. acrolein) and therapeutic drugs (e.
View Article and Find Full Text PDFHumans have extensive adverse exposure to alpha,beta-unsaturated carbonyl compounds (ABuCs) as these are major toxins in smoke and exhaust fumes, as well as products of lipid peroxidation. In contrast, another ABuC, dimethylfumarate, is used to treat psoriasis and multiple sclerosis. ABuCs undergo Michael adduction with amine, imidazole and thiol groups, with reaction at Cys residues predominating.
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