As a method of studying the cellular effects in hyperglycemic conditions, photocaged carbohydrates are being synthesized to control cytokine production. O-linked N-acetylglucosamine (O-GlcNAc), a monosaccharide derived from Glucose, is crucial to a multitude of metabolic processes (i.e. transcription, translation, nuclear transport, etc.). The post translational modification of O-GlcNacylation adds O-GlcNAc to a signaling protein at a serine or threonine site. In strained cell conditions, such modifications have a direct impact on internuclear cytokine levels. As the field develops greater knowledge of O-GlcNAcylation and its effects, stronger connections between cytokine overproduction and fatalities from hyperglycemia, a toxic event in conditions like diabetes mellitus, can be made. Currently, there is little known about what initiates unrestrained cytokine production as a response to cellular stress. In order for an inflammatory response of cytokines to occur it can be suspected that transcription factors are altered by O-GlcNAcylation to persuade its movement to the nucleus. Such nuclear translocation catalyzes cytokine production. This project identifies a chemical strategy to control GlcNAc elevation, effecting transcription factor nuclear relocation and cytokine levels. Specifically, transcription factor, NF-kB, serves as a model cytokine promoting protein that responds to hyperglycemia. Photocages, are light sensitive synthetic molecules used to harness reactivity of biological components. Once chemically bound to sugars, like O-GlcNAc or Glucose, it is of interest to determine their ability to control nuclear translocation of transcription factors, followed by nuclear cytokine synthesis. This will be accomplished by successfully synthesizing Glucose photocages, determining its decaging capabilities, then applying them to a variety of cell lines. Since Glucose is the predecessor of O-GlcNAc, we must gauge its photocage abilities to widen our scope of understanding towards these tools. Gaining depth in the versatility of photocaged carbohydrates, necessary for cellular maintenance, will encourage new directions of medicinal treatments.

Photocaged glucose strategy to dissect sugar-driven cellular cytokine production

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.