Developing a Mitochondria-Targeting Azide-based 1,8-Naphthalimide Probe for Hydrogen Sulfide Sensing
Reaction-based small-molecule fluorescent probes show great promise as diagnostic tools. Hydrogen sulfide has recently emerged as a signalling molecule closely associated with mitochondria within the cell. The aim of this project was to develop a turn-on mitochondria-targeting hydrogen sulfide probe, based on the reduction of an azide moiety attached to a 1,8-naphthalimide scaffold. Peptide sequences similar to mitochondria-penetrating peptides were assembled using solid-phase peptide synthesis. The fluorescence intensity of the 1,8-napthalimide probe conjugated to the peptides increased over 60 minutes when treated with a hydrogen sulfide source. Thiazole orange was also coupled to the peptides in order to investigate the localisation of the peptides within the cell. Cellular uptake of all peptide conjugates was low and localisation studies were inconclusive. In future studies, altering the stereochemistry of the arginine residues of the peptide sequences to the unnatural D-enantiomer may improve cellular uptake.