Articles producció científica> Enginyeria Electrònica, Elèctrica i Automàtica

Selection of an Aptamer against the Enzyme 1-deoxy-D-xylulose-5-phosphate Reductoisomerase from Plasmodium falciparum

  • Datos identificativos

    Identificador: imarina:9287713
    Autores:
    Roca, CarlotaAvalos-Padilla, YunuenPrieto-Simon, BeatrizIglesias, ValentinRamirez, MiriamImperial, SantiagoFernandez-Busquets, Xavier
    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.
  • Otros:

    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
  • Palabras clave:

    Pharmaceutical Science,Pharmacology & Pharmacy
    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
    Pharmacology & pharmacy
    Pharmaceutical science
    Medicina ii
    Farmacia
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
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