title: Targeting G-quadruplex structure in the human c-Kit promoter with short PNA sequences.
abstract: The cKit87up sequence d((5')AGGGAGGGCGCTGGGAGGAGGG(3')) can form a unique G-quadruplex structure in the promoter region of the human c-kit protooncogene. It provides a peculiar platform for the design of selective quadruplex-binding agents, which could potentially repress the protooncogene transcription. In this study, we examined the binding of a small library of PNA probes (P1-P5) targeting cKit87up quadruplex in either K(+)- or NH(4)(+)-containing solutions by using a combination of UV, CD, PAGE, ITC, and ESI-MS methodologies. Our results showed that (1) P1-P4 interact with the cKit87up quadruplex, and (2) the binding mode depends on the quadruplex stability. In K(+) buffer, P1-P4 bind the ckit87up quadruplex structure as "quadruplex-binding agents". The same holds for P1 in NH(4)(+) solution. On the contrary, in NH(4)(+) solution, P2-P4 overcome the quadruplex structure by forming PNA/DNA hybrid complexes, thus acting as "quadruplex openers".
authors.affiliation: Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II , via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Jussara
authors.initials: J
authors.lastname: Amato
authors.forename: Bruno
authors.initials: B
authors.lastname: Pagano
authors.forename: Nicola
authors.initials: N
authors.lastname: Borbone
authors.forename: Giorgia
authors.initials: G
authors.lastname: Oliviero
authors.forename: Valérie
authors.initials: V
authors.lastname: Gabelica
authors.forename: Edwin De
authors.initials: ED
authors.lastname: Pauw
authors.forename: Stefano
authors.initials: S
authors.lastname: D'Errico
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Piccialli
authors.forename: Michela
authors.initials: M
authors.lastname: Varra
authors.forename: Concetta
authors.initials: C
authors.lastname: Giancola
authors.forename: Gennaro
authors.initials: G
authors.lastname: Piccialli
authors.forename: Luciano
authors.initials: L
authors.lastname: Mayol
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D015345:Oligonucleotide Probes / Q000138:chemical synthesis / Q000737:chemistry*; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry*
chemical_list: D015345:Oligonucleotide Probes; D020135:Peptide Nucleic Acids; D019009:Proto-Oncogene Proteins c-kit