Niemann-Pick type C (NPC) is a lysosomal storage disease caused by mutations of the NPC1 and NPC2 genes with an estimated frequency of 1:150,000 people. Deficiency in functions of NPC1 or NPC2 proteins results in accumulation of unesterified cholesterol in lysosomes of defective cells. Currently there are no FDA-approved therapies for NPC. Recent studies showed that tocopherol, an antioxidant agent, effectively decreased lysosomal cholesterol accumulation and lysosomal volume as well as increased cholesterol efflux. Reduction of these abnormalities may be mediated through a tocopherol-induced intracellular Ca2+ response and subsequent increment of lysosomal exocytosis. In order to further investigate mechanisms of cellular cholesterol trafficking, several fluorescent tocopherol probes were designed and synthesized by utilization of different dyes, linkers and labeling positions. Herein we present the detailed background, design and syntheses of the fluorescent tocopherol probes.

Design and syntheses of multiple fluorescent tocopherol probes

248th National Meeting (2014)

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