Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure

Evonne M. Rezler, Jeyaprakashnarayanan Seenisamy, Sridevi Bashyam, Mu Yong Kim, Elizabeth White, W. David Wilson, Laurence Hurley

Research output: Contribution to journalArticle

288 Citations (Scopus)

Abstract

The human telomeric sequence d[T2AG3]4 has been demonstrated to form different types of G-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-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-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 structure with 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 Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce 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 significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.

Original languageEnglish (US)
Pages (from-to)9439-9447
Number of pages9
JournalJournal of the American Chemical Society
Volume127
Issue number26
DOIs
StatePublished - Jul 6 2005

Fingerprint

G-Quadruplexes
Ligands
Dichroism
Stoichiometry
Monovalent Cations
Oligonucleotides
Surface plasmon resonance
Propellers
Genetic Promoter Regions
Biosensors
Potassium
Conformations
Chlorides
Assays
Stabilization
Positive ions
Sodium
Circular Dichroism
telomestatin
sapphyrin

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure. / Rezler, Evonne M.; Seenisamy, Jeyaprakashnarayanan; Bashyam, Sridevi; Kim, Mu Yong; White, Elizabeth; Wilson, W. David; Hurley, Laurence.

In: Journal of the American Chemical Society, Vol. 127, No. 26, 06.07.2005, p. 9439-9447.

Research output: Contribution to journalArticle

Rezler, Evonne M. ; Seenisamy, Jeyaprakashnarayanan ; Bashyam, Sridevi ; Kim, Mu Yong ; White, Elizabeth ; Wilson, W. David ; Hurley, Laurence. / Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure. In: Journal of the American Chemical Society. 2005 ; Vol. 127, No. 26. pp. 9439-9447.
@article{b4165ec4b532446cbb83b8f72acc772c,
title = "Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure",
abstract = "The human telomeric sequence d[T2AG3]4 has been demonstrated to form different types of G-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-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-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 structure with 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 Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce 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 significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.",
author = "Rezler, {Evonne M.} and Jeyaprakashnarayanan Seenisamy and Sridevi Bashyam and Kim, {Mu Yong} and Elizabeth White and Wilson, {W. David} and Laurence Hurley",
year = "2005",
month = "7",
day = "6",
doi = "10.1021/ja0505088",
language = "English (US)",
volume = "127",
pages = "9439--9447",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "26",

}

TY - JOUR

T1 - Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure

AU - Rezler, Evonne M.

AU - Seenisamy, Jeyaprakashnarayanan

AU - Bashyam, Sridevi

AU - Kim, Mu Yong

AU - White, Elizabeth

AU - Wilson, W. David

AU - Hurley, Laurence

PY - 2005/7/6

Y1 - 2005/7/6

N2 - The human telomeric sequence d[T2AG3]4 has been demonstrated to form different types of G-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-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-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 structure with 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 Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce 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 significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.

AB - The human telomeric sequence d[T2AG3]4 has been demonstrated to form different types of G-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-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-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 structure with 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 Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce 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 significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.

UR - http://www.scopus.com/inward/record.url?scp=21644460419&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21644460419&partnerID=8YFLogxK

U2 - 10.1021/ja0505088

DO - 10.1021/ja0505088

M3 - Article

C2 - 15984871

AN - SCOPUS:21644460419

VL - 127

SP - 9439

EP - 9447

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 26

ER -