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

被引：40

作者：

Amato, Jussara ^{[1
]}

Pagano, Bruno ^{[2
]}

Borbone, Nicola ^{[1
]}

Oliviero, Giorgia ^{[1
]}

Gabelica, Valerie ^{[3
]}

De Pauw, Edwin ^{[3
]}

D'Errico, Stefano ^{[1
]}

Piccialli, Vincenzo ^{[4
]}

Varra, Michela ^{[1
]}

Giancola, Concetta ^{[5
]}

Piccialli, Gennaro ^{[1
]}

Mayol, Luciano ^{[1
]}

机构：

[1] Univ Naples Federico II, Dipartimento Chim Sostanze Nat, I-80131 Naples, Italy

[2] Univ Salerno, Dipartimento Sci Farmaceut, I-84084 Fisciano, SA, Italy

[3] Univ Liege, Dept Chem, Phys Chem & Mass Spectrometry Lab, B-4000 Liege, Belgium

[4] Univ Naples Federico II, Dipartimento Chim Organ & Biochim, I-80126 Naples, Italy

[5] Univ Naples Federico II, Dipartimento Chim P Corradini, I-80126 Naples, Italy

来源：

BIOCONJUGATE CHEMISTRY | 2011年 / 22卷 / 04期

关键词：

ELECTROSPRAY MASS-SPECTROMETRY; SMALL-MOLECULE; NUCLEIC-ACIDS; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; NUCLEOTIDE CHEMISTRY; STRAND DISPLACEMENT; CIRCULAR-DICHROISM; GENE-EXPRESSION; MYC PROMOTER; HUMAN GENOME;

D O I：

10.1021/bc100444v

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The cKit87up sequence d((5')AGGGAGGGCGC-TGGGAGGAGGG(3')) can form a unique G-quadruplex structure in the promoter region of the human c-kit protooncogene. It pro rules 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 NH4+-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 PI in NH4+ solution. On the contrary, in NH4+ solution, P2-P4 overcome the quadruplex structure by forming PNA/DNA hybrid complexes, thus acting as "quadruplex openers".

引用

页码：654 / 663

页数：10

共 51 条

[1] Hybridization of Short Complementary PNAs to G-Quadruplex Forming Oligonucleotides: An Electrospray Mass Spectrometry Study [J].