Targeting G-Quadruplex Structure in the Human c-Kit Promoter with Short PNA Sequences
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- 作者：Jussara Amato ; Bruno Pagano ; Nicola Borbone ; Giorgia Oliviero ; Vale虂rie Gabelica ; Edwin De Pauw ; Stefano D鈥橢rrico ; Vincenzo Piccialli ; Michela Varra ; Concetta Giancola ; Gennaro Piccialli ; Luciano Mayol
- 刊名：Bioconjugate Chemistry
- 出版年：2011
- 出版时间：April 20, 2011
- 年：2011
- 卷：22
- 期：4
- 页码：654-663
- 全文大小：966K
- 年卷期：v.22,no.4(April 20, 2011)
- ISSN：1520-4812
文摘
The cKit87up sequence d(5鈥?/sup>AGGGAGGGCGCTGGGAGGAGGG3鈥?/sup>) 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鈭扨5) 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鈭扨4 interact with the cKit87up quadruplex, and (2) the binding mode depends on the quadruplex stability. In K+ buffer, P1鈭扨4 bind the ckit87up quadruplex structure as 鈥渜uadruplex-binding agents鈥? The same holds for P1 in NH4+ solution. On the contrary, in NH4+ solution, P2鈭扨4 overcome the quadruplex structure by forming PNA/DNA hybrid complexes, thus acting as 鈥渜uadruplex openers鈥?