Person:
Pingarrón Carrazón, José Manuel

Profile Picture
First Name
José Manuel
Last Name
Pingarrón Carrazón
URI
https://hdl.handle.net/20.500.14352/76312
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Area
Química Analítica
Identifiers
UCM identifierORCIDScopus Author IDWeb of Science ResearcherIDDialnet IDGoogle Scholar ID

Filters

20192
Reset filters

Settings

End date: 2019 × Subject: 577.1 ×

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    11PS04 is a new chemical entity identified by microRNA-based biosensing with promising therapeutic potential against cancer stem cells
    (Scientific Reports, 2019) Aguado Sánchez, Tania; Romero-Revilla, José A.; Granados, Rosario; Campuzano Ruiz, Susana; Torrente Rodríguez, Rebeca Magnolia; Cuesta Martínez, Ángel; Albiñana, Virginia; Botella, Luisa María; Santamaría, Silvia; Garcia-Sanz, Jose A.; Pingarrón Carrazón, José Manuel; Sánchez-Sancho, Francisco; Sánchez-Puelles, José-María
    Phenotypic drug discovery must take advantage of the large amount of clinical data currently available. In this sense, the impact of microRNAs (miRs) on human disease and clinical therapeutic responses is becoming increasingly well documented. Accordingly, it might be possible to use miR-based signatures as phenotypic read-outs of pathological status, for example in cancer. Here, we propose to use the information accumulating regarding the biology of miRs from clinical research in the preclinical arena, adapting it to the use of miR biosensors in the earliest steps of drug screening. Thus, we have used an amperometric dual magnetosensor capable of monitoring a miR-21/miR-205 signature to screen for new drugs that restore these miRs to non-tumorigenic levels in cell models of breast cancer and glioblastoma. In this way we have been able to identify a new chemical entity, 11PS04 ((3aR,7aS)-2-(3-propoxyphenyl)-7,7a-dihydro-3aH-pyrano[3,4-d]oxazol-6(4H)-one), the therapeutic potential of which was suggested in mechanistic assays of disease models, including 3D cell culture (oncospheres) and xenografts. These assays highlighted the potential of this compound to attack cancer stem cells, reducing the growth of breast and glioblastoma tumors in vivo. These data demonstrate the enhanced chain of translatability of this strategy, opening up new perspectives for drug-discovery pipelines and highlighting the potential of miR-based electro-analytical sensors as efficient tools in modern drug discovery.
  • Thumbnail Image
    Item
    Hairpin DNA-AuNPs as molecular binding elements for the detection of volatile organic compounds
    (Biosensors and Bioelectronics, 2019) Mascini, Marcello; Gaggiotti, Sara; Della Pelle, Flavio; Wang, Joseph; Pingarrón Carrazón, José Manuel; Compagnone, Dario
    Hairpin DNA (hpDNA) loops were used for the first time as molecular binding elements in gas analysis. The hpDNA loops sequences of unpaired bases were studied in-silico to evaluate the binding versus four chemical classes (alcohols, aldehydes, esters and ketones) of volatile organic compounds (VOCs). The virtual binding score trend was correlated to the oligonucleotide size and increased of about 25% from tetramer to hexamer. Two tetramer and pentamer and three hexamer loops were selected to test the recognition ability of the DNA motif. The selection was carried out trying to maximize differences among chemical classes in order to evaluate the ability of the sensors to work as an array. All oligonucleotides showed similar trends with best binding scores for alcohols followed by esters, aldehydes and ketones. The seven ssDNA loops (CCAG, TTCT, CCCGA, TAAGT, ATAATC, CATGTC and CTGCAA) were then extended with the same double helix stem of four base pair DNA (GAAG to 5′ end and CTTC to 3′ end) and covalently bound to gold nanoparticles (AuNPs) using a thiol spacer attached to 5′ end of the hpDNA. HpDNA-AuNPs were deposited onto 20 MHz quartz crystal microbalances (QCMs) to form the gas piezoelectric sensors. An estimation of relative binding affinities was obtained using different amounts of eight VOCs (ethanol, 3-methylbutan-1-ol, 1-pentanol, octanal, nonanal, ethyl acetate, ethyl octanoate, and butane-2,3-dione) representative of the four chemical classes. In agreement with the predicted simulation, hexamer DNA loops improved by two orders of magnitude the binding affinity highlighting the key role of the hpDNA loop size. Using the sensors as an array a clear discrimination of VOCs on the basis of molecular weight and functional groups was achieved, analyzing the experimental with principal components analysis (PCA) demonstrating that HpDNA is a promising molecular binding element for analysis of VOCs.