التفاصيل البيبلوغرافية
| العنوان: |
A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in Plasmodium falciparum |
| المؤلفون: |
Romain Duval, Kevin Cottet, Magali Blaud, Anaïs Merckx, Sandrine Houzé, Philippe Grellier, Marie-Christine Lallemand, Sylvie Michel |
| المصدر: |
Molecules; Volume 25; Issue 21; Pages: 5139 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2020 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
Guttiferone A, Plasmodium falciparum, 7-azidocoumarin, photoactivation, fluorogenesis |
| جغرافية الموضوع: |
agris |
| الوصف: |
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. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Chemical Biology; https://dx.doi.org/10.3390/molecules25215139 |
| DOI: |
10.3390/molecules25215139 |
| الاتاحة: |
https://doi.org/10.3390/molecules25215139 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.8750C26A |
| قاعدة البيانات: |
BASE |