New nucleotide-competitive non-nucleoside inhibitors of terminal deoxynucleotidyl transferase: Discovery, characterization, and crystal structure in complex with the target (Articolo in rivista)

Type
Label
  • New nucleotide-competitive non-nucleoside inhibitors of terminal deoxynucleotidyl transferase: Discovery, characterization, and crystal structure in complex with the target (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/jm4010187 (literal)
Alternative label
  • Costi R, Cuzzucoli Crucitti G, Pescatori L, Messore A, Scipione L, Tortorella S, Amoroso A, Crespan E, Campiglia P, Maresca B, Porta A, Granata I, Novellino E, Gouge J, Delarue M, Maga G, Di Santo R. (2013)
    New nucleotide-competitive non-nucleoside inhibitors of terminal deoxynucleotidyl transferase: Discovery, characterization, and crystal structure in complex with the target
    in Journal of medicinal chemistry (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Costi R, Cuzzucoli Crucitti G, Pescatori L, Messore A, Scipione L, Tortorella S, Amoroso A, Crespan E, Campiglia P, Maresca B, Porta A, Granata I, Novellino E, Gouge J, Delarue M, Maga G, Di Santo R. (literal)
Pagina inizio
  • 7431 (literal)
Pagina fine
  • 7441 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.scopus.com/inward/record.url?eid=2-s2.0-84885013896&partnerID=q2rCbXpz (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 56 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 18 (literal)
Note
  • Scopu (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Dipartimento di Chimica e Tecnologie Del Farmaco, Istituto Pasteur - Fondazione Cenci Bolognetti, Sapienza Università di Roma, P.le Aldo Moro 5, I-00185 Roma, Italy; Institute of Molecular Genetics IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy; Department of Pharmaceutical and BioMedical Sciences, University of Salerno, I-84084 Fisciano, Salerno, Italy; Dipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano 49, I-80131 Napoli, Italy; Dynamique Structurale des Macromolecules, UMR 3528, CNRS, Institut Pasteur, 25 Rue du Dr Roux, 75015 Paris, France (literal)
Titolo
  • New nucleotide-competitive non-nucleoside inhibitors of terminal deoxynucleotidyl transferase: Discovery, characterization, and crystal structure in complex with the target (literal)
Abstract
  • Terminal deoxynucletidyl transferase (TdT) is overexpressed in some cancer types, where it might compete with pol ? during the mutagenic repair of double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. Here we report the discovery and characterization of pyrrolyl and indolyl diketo acids that specifically target TdT and behave as nucleotide-competitive inhibitors. These compounds show a selective toxicity toward MOLT-4 compared to HeLa cells that correlate well with in vitro selectivity for TdT. The binding site of two of these inhibitors was determined by cocrystallization with TdT, explaining why these compounds are competitive inhibitors of the deoxynucleotide triphosphate (dNTP). In addition, because of the observed dual localization of the phenyl substituent, these studies open the possibility of rationally designing more potent compounds. © 2013 American Chemical Society. (literal)
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