Počet záznamů: 1
G-Quadruplex Identification in the Genome of Protozoan Parasites Points to Naphthalene Diimide Ligands as New Antiparasitic Agents
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SYSNO ASEP 0488390 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název G-Quadruplex Identification in the Genome of Protozoan Parasites Points to Naphthalene Diimide Ligands as New Antiparasitic Agents Tvůrce(i) Belmonte-Reche, E. (ES)
Martínez-García, M. (ES)
Guédin, A. (FR)
Zuffo, M. (IT)
Arevalo-Ruiz, M. (ES)
Doria, F. (IT)
Campos-Salinas, J. (ES)
Maynadier, M. (FR)
Lopez-Rubio, J.J. (FR)
Freccero, M. (IT)
Mergny, Jean-Louis (BFU-R) ORCID, RID
Maria Perez-Victoria, J. (ES)
Carlos Morales, J. (ES)Celkový počet autorů 13 Zdroj.dok. Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623
Roč. 61, č. 3 (2018), s. 1231-1240Poč.str. 10 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova terminal repeat promoter ; plasmodium-falciparum Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP EF15_003/0000477 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora BFU-R - RVO:68081707 UT WOS 000425063400041 DOI 10.1021/acs.jmedchem.7b01672 Anotace G-quadruplexes (G4) are DNA secondary structures that take part in the regulation of gene expression. Putative G4 forming sequences (PQS) have been reported in mammals, yeast, bacteria, and viruses. Here, we present PQS searches on the genomes of T. brucei, L. major, and P. falciparum. We found telomeric sequences and new PQS motifs. Biophysical experiments showed that EBR1, a 29 nucleotide long highly repeated PQS in T. brucei, forms a stable G4 structure. G4 ligands based on carbohydrate conjugated naphthalene diimides (carb-NDIs) that bind G4's including hTel could bind EBR1 with selectivity versus dsDNA. These ligands showed important antiparasitic activity. IC50 values were in the nanomolar range against T. brucei with high selectivity against MRC-5 human cells. Confocal microscopy confirmed these ligands localize in the nucleus and kinetoplast of T. brucei suggesting they can reach their potential G4 targets. Cytotoxicity and zebrafish toxicity studies revealed sugar conjugation reduces intrinsic toxicity of NDIs. Pracoviště Biofyzikální ústav Kontakt Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Rok sběru 2018
Počet záznamů: 1