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".

Targeting G-Quadruplex Structure in the Human c-Kit Promoter with Short PNA Sequences / Amato, Jussara; Pagano, Bruno; Borbone, Nicola; Oliviero, Giorgia; V., Gabelica; E., De Pauw; D'Errico, Stefano; Piccialli, Vincenzo; Varra, Michela; Giancola, Concetta; Piccialli, Gennaro; Mayol, Luciano. - In: BIOCONJUGATE CHEMISTRY. - ISSN 1043-1802. - 22:4(2011), pp. 654-663. [10.1021/bc100444v]

Targeting G-Quadruplex Structure in the Human c-Kit Promoter with Short PNA Sequences

AMATO, JUSSARA;PAGANO, BRUNO;BORBONE, NICOLA;OLIVIERO, GIORGIA;D'ERRICO, STEFANO;PICCIALLI, VINCENZO;VARRA, MICHELA;GIANCOLA, CONCETTA;PICCIALLI, GENNARO;MAYOL, LUCIANO
2011

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".
2011
Targeting G-Quadruplex Structure in the Human c-Kit Promoter with Short PNA Sequences / Amato, Jussara; Pagano, Bruno; Borbone, Nicola; Oliviero, Giorgia; V., Gabelica; E., De Pauw; D'Errico, Stefano; Piccialli, Vincenzo; Varra, Michela; Giancola, Concetta; Piccialli, Gennaro; Mayol, Luciano. - In: BIOCONJUGATE CHEMISTRY. - ISSN 1043-1802. - 22:4(2011), pp. 654-663. [10.1021/bc100444v]
File in questo prodotto:
File Dimensione Formato  
bc100444v.pdf

accesso aperto

Tipologia: Altro materiale allegato
Licenza: Dominio pubblico
Dimensione 965.64 kB
Formato Adobe PDF
965.64 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/393173
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 43
  • ???jsp.display-item.citation.isi??? 41
social impact