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Article

A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in Plasmodium falciparum

1
Université de Paris, MERIT, IRD, F-75006 Paris, France
2
Université de Paris, CiTCoM, CNRS, F-75006 Paris, France
3
CNR du Paludisme, AP-HP, Hôpital Bichat—Claude-Bernard, F-75018 Paris, France
4
Unité Molécules de Communication et Adaptation des Microorganismes (MCAM), UMR 7245, CNRS Muséum National d’Histoire Naturelle, F-75005 Paris, France
*
Author to whom correspondence should be addressed.
Academic Editor: James T. Hodgkinson
Molecules 2020, 25(21), 5139; https://doi.org/10.3390/molecules25215139
Received: 30 September 2020 / Revised: 29 October 2020 / Accepted: 30 October 2020 / Published: 4 November 2020
(This article belongs to the Special Issue Chemical Probe Synthesis and Applications in Chemical Biology)
Guttiferone A (GA) 1, a polycyclic polyprenylated acylphloroglucinol (PPAP) isolated from the plant Symphonia globulifera (Clusiaceae), constitutes a novel hit in antimalarial drug discovery. PPAPs do not possess identified biochemical targets in malarial parasites up to now. Towards this aim, we designed and evaluated a natural product-derived photoactivatable probe AZC-GA 5, embedding a photoalkylative fluorogenic motif of the 7-azidocoumarin (AZC) type, devoted to studying the affinity proteins interacting with GA in Plasmodium falciparum. Probe 5 manifested a number of positive functional and biological features, such as (i) inhibitory activity in vitro against P. falciparum blood-stages that was superimposable to that of GA 1, dose–response photoalkylative fluorogenic properties (ii) in model conditions using bovine serum albumin (BSA) as an affinity protein surrogate, (iii) in live P. falciparum-infected erythrocytes, and (iv) in fresh P. falciparum cell lysate. Fluorogenic signals by photoactivated AZC-GA 5 in biological settings were markedly abolished in the presence of excess GA 1 as a competitor, indicating significant pharmacological specificity of the designed molecular probe relative to the native PPAP. These results open the way to identify the detected plasmodial proteins as putative drug targets for the natural product 1 by means of proteomic analysis. View Full-Text
Keywords: Guttiferone A; Plasmodium falciparum; 7-azidocoumarin; photoactivation; fluorogenesis Guttiferone A; Plasmodium falciparum; 7-azidocoumarin; photoactivation; fluorogenesis
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MDPI and ACS Style

Duval, R.; Cottet, K.; Blaud, M.; Merckx, A.; Houzé, S.; Grellier, P.; Lallemand, M.-C.; Michel, S. A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in Plasmodium falciparum. Molecules 2020, 25, 5139. https://doi.org/10.3390/molecules25215139

AMA Style

Duval R, Cottet K, Blaud M, Merckx A, Houzé S, Grellier P, Lallemand M-C, Michel S. A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in Plasmodium falciparum. Molecules. 2020; 25(21):5139. https://doi.org/10.3390/molecules25215139

Chicago/Turabian Style

Duval, Romain, Kevin Cottet, Magali Blaud, Anaïs Merckx, Sandrine Houzé, Philippe Grellier, Marie-Christine Lallemand, and Sylvie Michel. 2020. "A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in Plasmodium falciparum" Molecules 25, no. 21: 5139. https://doi.org/10.3390/molecules25215139

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