Telomestatin and Diseleno Sapphyrin Bind Selectively to Two Different Forms of the Human Telomeric G-Quadruplex Structure

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• 作者：Evonne M. Rezler ; Jeyaprakashnarayanan Seenisamy ; Sridevi Bashyam ; Mu-Yong Kim ; Elizabeth White ; W. David Wilson ; and Laurence H. Hurley
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：July 6, 2005
• 年：2005
• 卷：127
• 期：26
• 页码：9439 - 9447
• 全文大小：479K
• 年卷期：v.127,no.26(July 6, 2005)
• ISSN：1520-5126

文摘

The human telomeric sequence d[T₂AG₃]₄ has been demonstrated to form different types ofG-quadruplex structures, depending upon the incubation conditions. For example, in sodium (Na⁺), a basket-type G-quadruplex structure is formed. In this investigation, using circular dichroism (CD), biosensor-surfaceplasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of differentG-quadruplex-binding ligands affects the conformation of the telomeric G-quadruplex found in solution.The results show that while telomestatin binds preferentially to the basket-type G-quadruplex structurewith a 2:1 stoichiometry, 5,10,15,20-[tetra-(N-methyl-3-pyridyl)]-26-28-diselena sapphyrin chloride (Se2SAP)binds to a different form with a 1:1 stoichiometry in potassium (K⁺). CD studies suggest that Se2SAPbinds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of astructure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it caninduce the formation of the basket-type G-quadruplex from a random coil human telomeric oligonucleotide,even in the absence of added monovalent cations such as K⁺ or Na⁺. In contrast, in the presence of K⁺,Se2SAP was found to convert the preformed basket G-quadruplex to the hybrid structure. The significanceof these results is that the presence of different ligands can determine the type of telomeric G-quadruplexstructures formed in solution. Thus, the biochemical and biological consequences of binding of ligands toG-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyondmere stabilization of these structures.