Abstract 1239 Non-polar amino acids as cellular uptake moieties for peroxisome targeting fluorophores

Peroxisomes are small, membrane-enclosed organelles found in eukaryotic cells, containing enzymes essential for various metabolic processes, including the breakdown of toxic substances and oxidative activities.Their functions are crucial to human health, as peroxisomal dysfunction is associated with several metabolic disorders, such as neurological abnormalities, defects in neuronal migration, and demyelination.Unfortunately, peroxisomes are extremely understudied.We believe developing chemical tools that can be used to examine peroxisomal functions would lead to a better understanding of the peroxisomes.Peroxisome Targeting Signals (PTS) are short amino acid sequences that direct proteins into peroxisomes and have been used to develop peroxisome-targeted fluorophores.Given the inherently polar nature of PTSs, small molecule peroxisome fluorescent probes delivered to the peroxisome in live cells are limited to those which have nonpolar fluorophores.To address this issue, a less polar PTS is being synthesized to improve cell permeability.Presently, efforts are focused on the synthesis of cell permeabilization moieties.It is hypothesized that coupling a more hydrophobic moiety to a PTS will improve enhance permeability while maintaining peroxisomal import.Here we present our efforts to develop a hydrophobic moiety to facilitate cell uptake of a polar fluorophore.Following chemical characterization, we deployed this in live cells to determine if this moiety can result in accumulation in cells.Current efforts are focused on optimizing uptake and once the best hydrophobic moiety is identified it will be combined with a PTS will to create cellpermeable chemical tools for studying peroxisome biochemsitry.