Since loss of function
mutations of PINK1 lead to early onset Parkinson’s
disease, there has been growing interest in the discovery of small
molecules that amplify the kinase activity of PINK1. We herein report
the design, synthesis, serum stability, and hydrolysis of four kinetin
riboside ProTides. These ProTides, along with kinetin riboside, activated
PINK1 in cells independent of mitochondrial depolarization. This highlights
the potential of modified nucleosides and their phosphate prodrugs
as treatments for neurodegenerative diseases.
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