Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization

[Image: see text] 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...

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Autores principales: 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., Mehellou, Youcef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410652/
https://www.ncbi.nlm.nih.gov/pubmed/28323427
http://dx.doi.org/10.1021/acs.jmedchem.6b01897
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author 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.
Mehellou, Youcef
author_facet 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.
Mehellou, Youcef
author_sort Osgerby, Laura
collection PubMed
description [Image: see text] 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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spelling pubmed-54106522017-05-02 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. Mehellou, Youcef J Med Chem [Image: see text] 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. American Chemical Society 2017-03-21 2017-04-27 /pmc/articles/PMC5410652/ /pubmed/28323427 http://dx.doi.org/10.1021/acs.jmedchem.6b01897 Text en Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle 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.
Mehellou, Youcef
Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
title Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
title_full Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
title_fullStr Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
title_full_unstemmed Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
title_short Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
title_sort kinetin riboside and its protides activate the parkinson’s disease associated pten-induced putative kinase 1 (pink1) independent of mitochondrial depolarization
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410652/
https://www.ncbi.nlm.nih.gov/pubmed/28323427
http://dx.doi.org/10.1021/acs.jmedchem.6b01897
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