Autor según el artículo: Roca, Carlota; Avalos-Padilla, Yunuen; Prieto-Simon, Beatriz; Iglesias, Valentin; Ramirez, Miriam; Imperial, Santiago; Fernandez-Busquets, Xavier;
Departamento: Enginyeria Electrònica, Elèctrica i Automàtica
Autor/es de la URV: Prieto Simón, Beatriz
Palabras clave: 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
Resumen: 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.
Áreas temáticas: Pharmacology & pharmacy Pharmaceutical science Medicina ii Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: beatriz.prieto-simon@urv.cat
Identificador del autor: 0000-0001-8016-1565
Fecha de alta del registro: 2024-09-07
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://www.mdpi.com/1999-4923/14/11/2515
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Pharmaceutics. 14 (11):
Referencia 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 del artículo: 10.3390/pharmaceutics14112515
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2022
Tipo de publicación: Journal Publications