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Kinetin riboside and its ProTides activate the Parkinson's Disease associated PTEN-Induced Putative Kinase 1 (PINK1) independent of mitochondrial depolarization

Osgerby, Laura, Lai, Yu-Chiang, Thornton, Peter J., Amalfitano, Joseph, Le Duff, Cécile S., Jabeen, Iqra, Kadri, Hachemi, Miccoli, Ageo, Tucker, James H. R., Muqit, Miratul M. K. and Mehellou, Youcef 2017. Kinetin riboside and its ProTides activate the Parkinson's Disease associated PTEN-Induced Putative Kinase 1 (PINK1) independent of mitochondrial depolarization. Journal of Medicinal Chemistry 60 (8) , pp. 3518-3524. 10.1021/acs.jmedchem.6b01897

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Abstract

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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Publisher: American Chemical Society
ISSN: 0022-2623
Date of First Compliant Deposit: 31 March 2017
Date of Acceptance: 21 March 2017
Last Modified: 21 Mar 2018 02:30
URI: http://orca.cf.ac.uk/id/eprint/99570

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