Research ArticleMalaria

Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay

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Science Translational Medicine  02 Jan 2019:
Vol. 11, Issue 473, eaau3174
DOI: 10.1126/scitranslmed.aau3174

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  • Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay
    • Dianne Sika-Paotonu, Associate Dean (Pacific)/Senior Lecturer Pathology & Molecular Medicine, Wellington School of Medicine & Health Sciences, University of Otago, New Zealand

    To the Editor,

    I read with interest the article published by Dziekan, J. M., et al. (1) and entitled: “Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay.”

    The decreasing responsiveness to antimalarial medications promotes an urgent need to better understand mechanisms of resistance, and also improve understanding of the mechanism of action (MoAs) for these drugs.

    This work sought to explore the MoAs for two antimalarial drugs using the combination of cellular thermal assay (CETSA) together with mass spectrometry (MS-CETSA) methods for drug target identification in Plasmodium falciparum – the main cause of malaria in humans.

    Initial validation work was undertaken.

    The MS-CETSA methodology was then used to investigate quinine and mefloquine. Quinine and mefloquine are two antimalarial medications currently in clinical use. There is however poor understanding concerning their respective antimalarial MoAs.

    Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) was identified as the common drug target for both these antimalarial drugs.

    One of the noted advantages of utilising MS-CETSA for drug target identification, was the ability to track direct biophysical binding to protein drug targets within the parasitic proteome allowing drug targets to be identified with minimal information concerning MOAs.

    An exciting and encouraging set of results demonstrating t...

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    Competing Interests: None declared.

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