Autor segons l'article: Roca, Carlota; Avalos-Padilla, Yunuen; Prieto-Simon, Beatriz; Iglesias, Valentin; Ramirez, Miriam; Imperial, Santiago; Fernandez-Busquets, Xavier;
Departament: Enginyeria Electrònica, Elèctrica i Automàtica
Autor/s de la URV: Prieto Simón, Beatriz
Paraules clau: Web server Protein-protein Plasmodium Pathway Methyl erythritol phosphate pathway Malaria Isoprenoid biosynthesis Inhibitors Evolution Drug targets Dna aptamers Apicoplast 1-deoxy-d-xylulose-5-phosphate reductoisomerase
Resum: The methyl erythritol phosphate (MEP) pathway of isoprenoid biosynthesis is essential for malaria parasites and also for several human pathogenic bacteria, thus representing an interesting target for future antimalarials and antibiotics and for diagnostic strategies. We have developed a DNA aptamer (D10) against Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme of this metabolic route. D10 binds in vitro to recombinant DXR from P. falciparum and Escherichia coli, showing at 10 mu M a ca. 50% inhibition of the bacterial enzyme. In silico docking analysis indicates that D10 associates with DXR in solvent-exposed regions outside the active center pocket. According to fluorescence confocal microscopy data, this aptamer specifically targets in P. falciparum in vitro cultures the apicoplast organelle where the MEP pathway is localized and is, therefore, a highly specific marker of red blood cells parasitized by Plasmodium vs. naive erythrocytes. D10 is also selective for the detection of MEP+ bacteria (e.g., E. coli and Pseudomonas aeruginosa) vs. those lacking DXR (e.g., Enterococcus faecalis). Based on these results, we discuss the potential of DNA aptamers in the development of ligands that can outcompete the performance of the well-established antibody technology for future therapeutic and diagnostic approaches.
Àrees temàtiques: Pharmacology & pharmacy Pharmaceutical science Medicina ii Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: beatriz.prieto-simon@urv.cat
Identificador de l'autor: 0000-0001-8016-1565
Data d'alta del registre: 2024-09-07
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Enllaç font original: https://www.mdpi.com/1999-4923/14/11/2515
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
Referència a l'article segons font original: Pharmaceutics. 14 (11):
Referència de l'ítem segons les normes APA: Roca, Carlota; Avalos-Padilla, Yunuen; Prieto-Simon, Beatriz; Iglesias, Valentin; Ramirez, Miriam; Imperial, Santiago; Fernandez-Busquets, Xavier; (2022). Selection of an Aptamer against the Enzyme 1-deoxy-D-xylulose-5-phosphate Reductoisomerase from Plasmodium falciparum. Pharmaceutics, 14(11), -. DOI: 10.3390/pharmaceutics14112515
DOI de l'article: 10.3390/pharmaceutics14112515
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2022
Tipus de publicació: Journal Publications